The DOI matches its Crossref record; 93 of the 94 references it cites were found in a registry or an index; none of the 126 sources its claims cite is checked for support yet.
The use of brain organoids to investigate neural development and disease
Open accessAbstract
Understanding the development and dysfunction of the human brain is a major goal of neurobiology. Much of our current understanding of human brain development has been derived from the examination of post-mortem and pathological specimens, bolstered by observations of developing non-human primates and experimental studies focused largely on mouse models. However, these tissue specimens and model systems cannot fully capture the unique and dynamic features of human brain development. Recent advances in stem cell technologies that enable the generation of human brain organoids from pluripotent stem cells (PSCs) promise to profoundly change our understanding of the development of the human brain and enable a detailed study of the pathogenesis of inherited and acquired brain diseases.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
76 Not checked yet · 36 Own interpretation · 2 No basis given
None of the sources cited for this claim have been checked yet.
In the paper
“The production of radial glial cells, intermediate progenitors, and deep- and superficial-layer neurons in an ordered temporal fashion has been reported by studies using all of the protocols currently in use2,3,5,25.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of development > Recapitulating aspects of human neurodevelopment
What the sources say
- Not checked yetcites [2] Lancaster, M. A. et al. Cerebral organoids model human brain development and microcephaly. Nature 501, 373–379 (2013). This was the first paper to introduce a method for generating cerebral organoids. The organoids were used to model microcephaly. source
- Not checked yetcites [3] Kadoshima, T. et al. Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex. Proc. Natl Acad. Sci. USA 110, 20284–20289 (2013). This study provided a detailed exploration of brain organoid tissue including the temporal and spatial organization of cell type diversity and patterning. source
- Not checked yetcites [5] Qian, X. et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell 165, 1238–1254 (2016). This study used mini bioreactors to produce forebrain organoids with a well-defined OSVZ and demonstrated the presence of oRGs with defined molecular markers. Diverse neuronal cell types expressing molecular markers of all six cortical layers were observed. source
- Not checked yetcites [25] Paşca, A. M. et al. Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nat. Methods 12, 671–678 (2015). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“However, protocols have also been published for the generation of organoids that model the development of other human brain regions, including the hippocampus7, midbrain4,5,8, hypothalamus5, cerebellum5,9, anterior pituitary10 and retina10,11.”
§ The use of brain organoids to investigate neural development and disease > Abstract
What the sources say
- Not checked yetcites [7] Sakaguchi, H. et al. Generation of functional hippocampal neurons from self-organizing human embryonic stem cell-derived dorsomedial telencephalic tissue. Nat. Commun. 6, 8896 (2015). source
- Not checked yetcites [4] Jo, J. et al. Midbrain-like organoids from human pluripotent stem cells contain functional dopaminergic and neuromelanin-producing neurons. Cell Stem Cell 19, 248–257 (2016). source
- Not checked yetcites [5] Qian, X. et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell 165, 1238–1254 (2016). This study used mini bioreactors to produce forebrain organoids with a well-defined OSVZ and demonstrated the presence of oRGs with defined molecular markers. Diverse neuronal cell types expressing molecular markers of all six cortical layers were observed. source
- Not checked yetcites [8] Monzel, A. S. et al. Derivation of human midbrain-specific organoids from neuroepithelial stem cells. Stem Cell Rep. 8, 1144–1154 (2017). source
- Not checked yetcites [9] Muguruma, K., Nishiyama, A., Kawakami, H., Hashimoto, K. & Sasai, Y. Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells. Cell Rep. 10, 537–550 (2015). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Most protocols therefore optimize neural induction by mimicking endogenous patterning through the application of exogenous cues (TABLE 1).”
§ The use of brain organoids to investigate neural development and disease > Generating organoids
What the sources say
- Not checked yetcites TABLE 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Nevertheless, several key features of in vivo brain organogenesis are recapitulated by in vitro organoids, making them attractive models for studies of certain aspects of brain development.”
§ The use of brain organoids to investigate neural development and disease > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Some protocols build on the principles of spontaneous neural induction by using medium that is free of neural induction signalling molecules2,27. This promotes the generation of diverse brain regions and cell populations2,28,29.”
§ The use of brain organoids to investigate neural development and disease > Generating organoids
What the sources say
- Not checked yetcites [2] Lancaster, M. A. et al. Cerebral organoids model human brain development and microcephaly. Nature 501, 373–379 (2013). This was the first paper to introduce a method for generating cerebral organoids. The organoids were used to model microcephaly. source
- Not checked yetcites [27] Lindborg, B. A. et al. Rapid induction of cerebral organoids from human induced pluripotent stem cells using a chemically defined hydrogel and defined cell culture medium. Stem Cells Transl Med. 5, 970–979 (2016). source
- Not checked yetcites [28] Quadrato, G. et al. Cell diversity and network dynamics in photosensitive human brain organoids. Nature 545, 48–53 (2017). This study analysed gene expression in over 80,000 individual cells and found that organoids can generate a broad diversity of cells that are related to endogenous classes, including cells from the cerebral cortex and the retina. Neuronal activity within organoids was also controlled using light stimulation of photosensitive cells. source
- Not checked yetcites [29] Camp, J. G. et al. Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc. Natl Acad. Sci. USA 112, 15672–15677 (2015). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“One important issue is that organoids derived from the same cell line under the same conditions can often produce tissues with different regional identities and spatial and cellular heterogeneity28,29.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of development
What the sources say
- Not checked yetcites [28] Quadrato, G. et al. Cell diversity and network dynamics in photosensitive human brain organoids. Nature 545, 48–53 (2017). This study analysed gene expression in over 80,000 individual cells and found that organoids can generate a broad diversity of cells that are related to endogenous classes, including cells from the cerebral cortex and the retina. Neuronal activity within organoids was also controlled using light stimulation of photosensitive cells. source
- Not checked yetcites [29] Camp, J. G. et al. Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc. Natl Acad. Sci. USA 112, 15672–15677 (2015). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Thus, human brain organoids could produce human-relevant cell types (as had been shown earlier in 2D PSC-derived cell cultures24), spurring an intense interest in organoid technologies as a model system to study human-specific features of brain development.”
§ The use of brain organoids to investigate neural development and disease > Generating organoids
What the sources say
- Not checked yetcites [24] Shi, Y., Kirwan, P. & Livesey, F. J. Directed differentiation of human pluripotent stem cells to cerebral cortex neurons and neural networks. Nat. Protoc. 7, 1836–1846 (2012). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Bioreactors designed to improve oxygen diffusion and nutrient distribution have been used to produce larger and more viable structures that can grow for longer periods2,5 (BOX 1).”
§ The use of brain organoids to investigate neural development and disease > Generating organoids
What the sources say
- Not checked yetcites [2] Lancaster, M. A. et al. Cerebral organoids model human brain development and microcephaly. Nature 501, 373–379 (2013). This was the first paper to introduce a method for generating cerebral organoids. The organoids were used to model microcephaly. source
- Not checked yetcites [5] Qian, X. et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell 165, 1238–1254 (2016). This study used mini bioreactors to produce forebrain organoids with a well-defined OSVZ and demonstrated the presence of oRGs with defined molecular markers. Diverse neuronal cell types expressing molecular markers of all six cortical layers were observed. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“It was also demonstrated that cell aggregation was not essential for efficient neural differentiation16, and a number of protocols for generating cortical neurons from monolayer cultures were developed17,18.”
§ The use of brain organoids to investigate neural development and disease > Generating organoids
What the sources say
- Not checked yetcites [16] Ying, Q.-L., Stavridis, M., Griffiths, D., Li, M. & Smith, A. Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture. Nat. Biotechnol. 21, 183–186 (2003). source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“A recent study further demonstrated the production of cortical neuron subtypes expressing markers found in all six cortical layers5 (FIG. 1).”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of development > Recapitulating aspects of human neurodevelopment
What the sources say
- Not checked yetcites [5] Qian, X. et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell 165, 1238–1254 (2016). This study used mini bioreactors to produce forebrain organoids with a well-defined OSVZ and demonstrated the presence of oRGs with defined molecular markers. Diverse neuronal cell types expressing molecular markers of all six cortical layers were observed. source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 36
- Probably not a substantial claim. 5
None of the sources cited for this claim have been checked yet.
In the paper
“Although such regional diversity is appealing, it also leads to a relatively variable outcome and the differentiation of some cells into non-ectodermal cell types28,29.”
§ The use of brain organoids to investigate neural development and disease > Generating organoids
What the sources say
- Not checked yetcites [28] Quadrato, G. et al. Cell diversity and network dynamics in photosensitive human brain organoids. Nature 545, 48–53 (2017). This study analysed gene expression in over 80,000 individual cells and found that organoids can generate a broad diversity of cells that are related to endogenous classes, including cells from the cerebral cortex and the retina. Neuronal activity within organoids was also controlled using light stimulation of photosensitive cells. source
- Not checked yetcites [29] Camp, J. G. et al. Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc. Natl Acad. Sci. USA 112, 15672–15677 (2015). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“WNT3A or a WNT pathway activator has therefore been used in combination with SMAD inhibition at early stages of forebrain organoid protocols, where it was found to promote production of neuroepithelial-like organoids and significantly reduce cell death5.”
§ The use of brain organoids to investigate neural development and disease > Generating organoids
What the sources say
- Not checked yetcites [5] Qian, X. et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell 165, 1238–1254 (2016). This study used mini bioreactors to produce forebrain organoids with a well-defined OSVZ and demonstrated the presence of oRGs with defined molecular markers. Diverse neuronal cell types expressing molecular markers of all six cortical layers were observed. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Similar to its in vivo patterning, inhibition of WNT signalling promotes anterior identity and enhances neurectodermal differentiation during early-stage embryoid body differentiation, whereas activation of WNT signalling posteriorizes the embryoid body and promotes mesoderm differentiation34.”
§ The use of brain organoids to investigate neural development and disease > Generating organoids
What the sources say
- Not checked yetcites [34] ten Berge, D. et al. Wnt signaling mediates self-organization and axis formation in embryoid bodies. Cell Stem Cell 3, 508–518 (2008). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly, the developmental timing of cortical neurogenesis appears to be conserved in vitro and has been demonstrated with both suspension and adherent differentiation methods2,3,5,39.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of development > Recapitulating aspects of human neurodevelopment
What the sources say
- Not checked yetcites [2] Lancaster, M. A. et al. Cerebral organoids model human brain development and microcephaly. Nature 501, 373–379 (2013). This was the first paper to introduce a method for generating cerebral organoids. The organoids were used to model microcephaly. source
- Not checked yetcites [3] Kadoshima, T. et al. Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex. Proc. Natl Acad. Sci. USA 110, 20284–20289 (2013). This study provided a detailed exploration of brain organoid tissue including the temporal and spatial organization of cell type diversity and patterning. source
- Not checked yetcites [5] Qian, X. et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell 165, 1238–1254 (2016). This study used mini bioreactors to produce forebrain organoids with a well-defined OSVZ and demonstrated the presence of oRGs with defined molecular markers. Diverse neuronal cell types expressing molecular markers of all six cortical layers were observed. source
- Not checked yetcites [39] Otani, T., Marchetto, M. C., Gage, F. H., Simons, B. D. & Livesey, F. J. 2D and 3D stem cell models of primate cortical development identify species-specific differences in progenitor behavior contributing to brain size. Cell Stem Cell 18, 467–480 (2016). source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Also, the authors observed that some cell types were only produced by a subset of organoids and that organoids grown in the same bioreactor tended to be similar in terms of their ability to make cells of each cluster, suggesting that batch effects and local microenvironments are important in patterning and possibly that organoids secrete signalling factors that influence sister organoids.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of development > Cell type diversity and reproducibility
What the sources say
- Not checked yetcites [28] Quadrato, G. et al. Cell diversity and network dynamics in photosensitive human brain organoids. Nature 545, 48–53 (2017). This study analysed gene expression in over 80,000 individual cells and found that organoids can generate a broad diversity of cells that are related to endogenous classes, including cells from the cerebral cortex and the retina. Neuronal activity within organoids was also controlled using light stimulation of photosensitive cells. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A recent study analysed DNA methylation in brain organoids and revealed that, although some patterns were conserved between fetal tissue and brain organoids, others were specific to in vitro conditions52.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of development > Modelling epigenomic remodelling
What the sources say
- Not checked yetcites [52] Luo, C. et al. Cerebral organoids recapitulate epigenomic signatures of the human fetal brain. Cell Rep. 17, 3369–3384 (2016). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“As one might expect, 6-month-old organoids presented a greater diversity of cell types than 3-month-old organoids, as well as enrichment of genes associated with neuronal and glial maturation.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of development > Cell type diversity and reproducibility
What the sources say
- Not checked yetcites [28] Quadrato, G. et al. Cell diversity and network dynamics in photosensitive human brain organoids. Nature 545, 48–53 (2017). This study analysed gene expression in over 80,000 individual cells and found that organoids can generate a broad diversity of cells that are related to endogenous classes, including cells from the cerebral cortex and the retina. Neuronal activity within organoids was also controlled using light stimulation of photosensitive cells. source
plaincorrelationaln = 31- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“For example, a large number of cells were assigned to a mesodermal lineage, emphasizing the variability inherent in the protocol.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of development > Cell type diversity and reproducibility
What the sources say
- Not checked yetcites [28] Quadrato, G. et al. Cell diversity and network dynamics in photosensitive human brain organoids. Nature 545, 48–53 (2017). This study analysed gene expression in over 80,000 individual cells and found that organoids can generate a broad diversity of cells that are related to endogenous classes, including cells from the cerebral cortex and the retina. Neuronal activity within organoids was also controlled using light stimulation of photosensitive cells. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Remarkably, these distinct subclasses of neuronal cells exhibited multilaminar organization, although they did not form the six distinct layers seen in normal mammalian cortex (FIG. 2a).”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of development > Recapitulating aspects of human neurodevelopment
What the sources say
- Not checked yetcites [5] Qian, X. et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell 165, 1238–1254 (2016). This study used mini bioreactors to produce forebrain organoids with a well-defined OSVZ and demonstrated the presence of oRGs with defined molecular markers. Diverse neuronal cell types expressing molecular markers of all six cortical layers were observed. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The cells that had migrated into the cortical spheroids also fired action potentials at twice the rate of cells in unfused subpallial spheres or non-migrated cells in the fused organoid, suggesting maturation of membrane properties.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of development > Establishing functional cortical circuits
What the sources say
- Not checked yetcites [6] Birey, F. et al. Assembly of functionally integrated human forebrain spheroids. Nature 545, 54–59 (2017). This study used pre-patterned pallial and subpallial spheroids to form fused forebrain spheroids, demonstrating interneuron diversity, migration and integration. This organoid model was used to model Timothy syndrome. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In the dorsal-ventral fused model mentioned earlier6, cells that migrated from the subpallial spheroid to the cortical spheroid expressed cortical interneuron markers, and whole-cell voltage-clamp recordings demonstrated that these interneuron-like cells can receive excitatory inputs from cells in the dorsal cortical organoids; conversely, the cells in the dorsal cortical organoids can receive”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of development > Establishing functional cortical circuits
What the sources say
- Not checked yetcites [6] Birey, F. et al. Assembly of functionally integrated human forebrain spheroids. Nature 545, 54–59 (2017). This study used pre-patterned pallial and subpallial spheroids to form fused forebrain spheroids, demonstrating interneuron diversity, migration and integration. This organoid model was used to model Timothy syndrome. source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Neurons fired action potentials spontaneously, there was evidence of synaptogenesis and excitatory postsynaptic potentials were evoked in response to extracellular electrical stimulation, suggesting neuronal connectivity.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of development > Establishing functional cortical circuits
What the sources say
- Not checked yetcites [25] Paşca, A. M. et al. Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nat. Methods 12, 671–678 (2015). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“For example, in embryogenesis, the effects of WNT signalling are stage specific, and there are divergent roles for WNT signalling in cell proliferation and cell type specification that depend on its temporal and regional expression (for reviews, see REFS 30,31).”
§ The use of brain organoids to investigate neural development and disease > Generating organoids
What the sources say
- Not checked yetcites [30] Suzuki, I. K. & Vanderhaeghen, P. Is this a brain which I see before me? Modeling human neural development with pluripotent stem cells. Development 142, 3138–3150 (2015). source
- Not checked yetcites [31] Harrison-Uy, S. J. & Pleasure, S. J. Wnt signaling and forebrain development. Cold Spring Harb. Perspect. Biol. 4, a008094 (2012).
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Despite differences in protocols, all organoids undergo some extent of self-organization; however, the mechanisms of self- organization are not well understood.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of development > Understanding self-organization
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A major limitation of organoid modelling is the lack of evidence of the establishment of faithful cortical circuits; however, some progress has been reported on this front.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of development > Establishing functional cortical circuits
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Organoids show structural features of ventricular zones and some aspects of cortical layering (FIG. 2a), but additional levels of cortical organization such as the radial glial scaffold, gyrification, proper cortical layering and the specificity of neuronal connections remain to be established and need to be compared to patterns observed in primary tissue (FIG. 3).”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of development > Challenges
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Cerebral organoids grown from these cells contained fewer proliferating progenitor cells and showed premature neural differentiation compared to wild-type counterparts.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of brain disease > Modelling neurodevelopmental disorders
What the sources say
- Not checked yetcites [2] Lancaster, M. A. et al. Cerebral organoids model human brain development and microcephaly. Nature 501, 373–379 (2013). This was the first paper to introduce a method for generating cerebral organoids. The organoids were used to model microcephaly. source
plaincorrelationalSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“oRGs are present in large numbers in gyrencephalic primates22,23,40–44 and are considered pivotal to the evolutionary increase in human cortex size and complexity45,46.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of development > Recapitulating aspects of human neurodevelopment
What the sources say
- Not checked yetcites [22] Fietz, S. A. et al. OSVZ progenitors of human and ferret neocortex are epithelial-like and expand by integrin signaling. Nat. Neurosci. 13, 690–699 (2010). source
- Not checked yetcites [23] Hansen, D. V., Lui, J. H., Parker, P. R. L. & Kriegstein, A. R. Neurogenic radial glia in the outer subventricular zone of human neocortex. Nature 464, 554–561 (2010). source
- Not checked yetcites [40] Smart, I. H. M., Dehay, C., Giroud, P., Berland, M. & Kennedy, H. Unique morphological features of the proliferative zones and postmitotic compartments of the neural epithelium giving rise to striate and extrastriate cortex in the monkey. Cereb. Cortex 12, 37–53 (2002). source
- Not checked yetcites [41] Lukaszewicz, A. et al. G1 phase regulation, area-specific cell cycle control, and cytoarchitectonics in the primate cortex. Neuron 47, 353–364 (2005). source
- Not checked yetcites [42] Zecevic, N., Chen, Y. & Filipovic, R. Contributions of cortical subventricular zone to the development of the human cerebral cortex. J. Comp. Neurol. 491, 109–122 (2005). source
- Not checked yetcites [43] Dehay, C. & Kennedy, H. Cell-cycle control and cortical development. Nat. Rev. Neurosci. 8, 438–450 (2007). source
- Not checked yetcites [44] Martínez- Cerdeño, V. et al. Comparative analysis of the subventricular zone in rat, ferret and macaque: evidence for an outer subventricular zone in rodents. PLoS ONE 7, e30178 (2012). source
- Not checked yetcites [45] Lui, J. H., Hansen, D. V. & Kriegstein, A. R. Development and evolution of the human neocortex. Cell 146, 18–36 (2011). source
- Not checked yetcites [46] Fish, J. L., Dehay, C., Kennedy, H. & Huttner, W. B. Making bigger brains-the evolution of neural-progenitor-cell division. J. Cell Sci. 121, 2783–2793 (2008). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This suggests that hem-like signalling centres can participate in the self-organization of cerebral organoids, mimicking the endogenous patterning of the developing brain.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of development > Understanding self-organization
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The brain organoid model is in an early phase of development.”
§ The use of brain organoids to investigate neural development and disease > Conclusions and future directions
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Studies using organoids and primary tissue both found high infectivity of NPCs; however, infection of astrocytes was only occasionally observed in organoids5 but was abundantly present in primary tissue72.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of brain disease > Modelling neurodevelopmental disorders
What the sources say
- Not checked yetcites [5] Qian, X. et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell 165, 1238–1254 (2016). This study used mini bioreactors to produce forebrain organoids with a well-defined OSVZ and demonstrated the presence of oRGs with defined molecular markers. Diverse neuronal cell types expressing molecular markers of all six cortical layers were observed. source
- Not checked yetcites [72] Retallack, H. et al. Zika virus cell tropism in the developing human brain and inhibition by azithromycin. Proc. Natl Acad. Sci. USA 113, 14408–14413 (2016). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“another study reporting that AXL is a crucial receptor for infection of human glial cells (astrocytes and microglia) but not of human NPCs75.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of brain disease > Modelling neurodevelopmental disorders
What the sources say
- Not checked yetcites [75] Meertens, L. et al. Axl mediates ZIKA virus entry in human glial cells and modulates innate immune responses. Cell Rep. 18, 324–333 (2017). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“single-cell RNA-seq data from human primary tissue revealed that the candidate viral entry receptor, AXL (also known as tyrosine-protein kinase receptor UFO), is highly expressed by human cortical radial glial cells, astrocytes, endothelial cells, and microglia, as well as in radial-glia-like cells of brain organoids73.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of brain disease > Modelling neurodevelopmental disorders
What the sources say
- Not checked yetcites [73] Nowakowski, T. J. et al. Expression analysis highlights AXL as a candidate zika virus entry receptor in neural stem cells. Cell Stem Cell 18, 591–596 (2016). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Blocking the AXL receptor reduced ZIKV infection of PSC-derived astrocytes in vitro, and genetic knockdown of AXL in a glial cell line nearly abolished infection.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of brain disease > Modelling neurodevelopmental disorders
What the sources say
- Not checked yetcites [73] Nowakowski, T. J. et al. Expression analysis highlights AXL as a candidate zika virus entry receptor in neural stem cells. Cell Stem Cell 18, 591–596 (2016). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The importance of AXL (or other receptors and pathways implicated in glial ZIKV infection) and the enhanced susceptibility of astrocytes and microglia to infection could have easily been overlooked based on brain organoid models alone, suggesting that more sophisticated organoids may be required for some aspects of disease modelling and drug discovery.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of brain disease > Modelling neurodevelopmental disorders
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Pathway analysis of gene expression changes during TLR3 activation highlighted several genes related to neuronal development, suggesting a mechanistic connection to disrupted neurogenesis.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of brain disease > Modelling neurodevelopmental disorders
What the sources say
- Not checked yetcites [71] Dang, J. et al. Zika virus depletes neural progenitors in human cerebral organoids through activation of the innate immune receptor TLR3. Cell Stem Cell 19, 258–265 (2016). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A second report also observed changes in the division mode of radial glial cells in MDS organoids and identified non-cell-autonomous defects in WNT signalling as an underlying mechanism67.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of brain disease > Modelling neurodevelopmental disorders
What the sources say
- Not checked yetcites [67] Iefremova, V. et al. An organoid-based model of cortical development identifies non-cell-autonomous defects in wnt signaling contributing to Miller–Dieker syndrome. Cell Rep. 19, 50–59 (2017). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“2D cell cultures may not provide the complex extracellular environment necessary to model extracellular protein aggregation, making 3D tissue-like structures an arguably more promising model.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of brain disease > Modelling neurodegenerative diseases
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of course, not all aspects of brain structure and function will be modelled by these tissue structures, but perhaps the most precocious events in disease aetiology can be captured and investigated, and these may share mechanistic pathways with disease features that manifest at later stages.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of brain disease > Modelling neurodegenerative diseases
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the absence of cell types involved with normal brain development and circuit function, the variation in structural features of cell and tissue architecture, and the need for more comprehensive transcriptional network matching between organoid and fetal tissue will need to be overcome to realize the full potential of these systems as models for human brain”
§ The use of brain organoids to investigate neural development and disease > Conclusions and future directions
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Further studies used forebrain organoids to reveal cell-specific viral tropism, selective effects on NPC proliferation5, and upregulation of the innate immune receptor Toll-like receptor 3 (TLR3) after ZIKV infection71.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of brain disease > Modelling neurodevelopmental disorders
What the sources say
- Not checked yetcites [5] Qian, X. et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell 165, 1238–1254 (2016). This study used mini bioreactors to produce forebrain organoids with a well-defined OSVZ and demonstrated the presence of oRGs with defined molecular markers. Diverse neuronal cell types expressing molecular markers of all six cortical layers were observed. source
- Not checked yetcites [71] Dang, J. et al. Zika virus depletes neural progenitors in human cerebral organoids through activation of the innate immune receptor TLR3. Cell Stem Cell 19, 258–265 (2016). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The amyloid hypothesis of AD posits that excessive accumulation of amyloid-β peptide leads to neurofibrillary tangles composed of aggregated hyperphosphorylated tau84.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of brain disease > Modelling neurodegenerative diseases
What the sources say
- Not checked yetcites [84] Serrano-Pozo, A., Frosch, M. P., Masliah, E. & Hyman, B. T. Neuropathological alterations in Alzheimer disease. Cold Spring Harb. Perspect. Med. 1, a006189 (2011). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The failure of many neurotherapeutic approaches to translate from animal models to clinical practice underscores the need for better predictive models, and brain organoids may help bridge this divide.”
§ The use of brain organoids to investigate neural development and disease > Conclusions and future directions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Brain organoids are amenable to drug treatment, and it has been shown that disease phenotypes can be recapitulated across multiple cell lines derived from different patients with AD.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of brain disease > Modelling neurodegenerative diseases
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Patient-derived organoids exhibited dysregulation of forkhead box G1 expression (an important gene for fore-brain development), accelerated cell cycle progression and increased production of GABAergic neurons.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of brain disease > Modelling psychiatric diseases
What the sources say
- Not checked yetcites [83] Mariani, J. et al. FOXG1-Dependent dysregulation of GABA/Glutamate neuron differentiation in autism spectrum disorders. Cell 162, 375–390 (2015). source
plaincorrelationaln = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“2D iPSC models have been important for analysing parameters such as gene expression, cell morphology, neuronal excitability, and synapse formation76,77 and have shed light on mechanisms underlying disorders such as schizophrenia78,79, bipolar disorder78–80, and Rett syndrome81”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of brain disease > Modelling psychiatric diseases
What the sources say
- Not checked yetcites [76] Wen, Z., Christian, K. M., Song, H. & Ming, G.-L. Modeling psychiatric disorders with patient-derived iPSCs. Curr. Opin. Neurobiol. 36, 118–127 (2016). source
- Not checked yetcites [77] Flaherty, E. K. & Brennand, K. J. Using hiPSCs to model neuropsychiatric copy number variations (CNVs) has potential to reveal underlying disease mechanisms. Brain Res. 1655, 283–293 (2017). source
- Not checked yetcites [78] Brennand, K. J. et al. Modelling schizophrenia using human induced pluripotent stem cells. Nature 473, 221–225 (2011). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The organoids also displayed severe apoptosis of neuroepithelial stem cells in the ventricular-like zone and a mitotic defect in oRGs50.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of brain disease > Modelling neurodevelopmental disorders
What the sources say
- Not checked yetcites [50] Bershteyn, M. et al. Human iPSC-derived cerebral organoids model cellular features of lissencephaly and reveal prolonged mitosis of outer radial glia. Cell Stem Cell 20, 435–449.e4 (2017). This study used brain organoids to model lissencephaly. The authors identified a mitotic defect in oRGs and used single-cell RNA sequencing to identify cells presenting an oRG transcriptional signature in human brain organoids. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The slow maturation of organoids may limit studies of later developmental events or stages of disease expression; however, disease phenotypes that manifest at early stages may be aptly modelled.”
§ The use of brain organoids to investigate neural development and disease > Conclusions and future directions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, they can also be used to discover human-specific phenotypes, providing an advantage over existing mouse models.”
§ The use of brain organoids to investigate neural development and disease > Organoids as models of brain disease > Modelling neurodevelopmental disorders
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Existing tissue specimens and model systems cannot fully capture the unique and dynamic features of human brain development.
“However, these tissue specimens and model systems cannot fully capture the unique and dynamic features of human brain development.”
The paper relies on this without support.
Organoid generation relies on the ability of stem and progenitor cells to self-organize to form complex tissue structures.
“Organoid generation relies on the remarkable ability of stem and progenitor cells to self-organize to form complex tissue structures.”
The paper relies on this without support.
Most human cortical circuits develop postnatally, and many take years to mature.
“Most human cortical circuits develop postnatally, and many take years to mature.”
The paper relies on this without support.
Animal models of neurodevelopmental diseases have species differences that limit their resemblance to human diseases.
“Although animal models of neurodevelopmental diseases have been essential for our current understanding of pathological mechanisms, there are obvious species differences that limit their resemblance to human diseases, including differences in developmental programmes, cytoarchitecture, cell composition, and genetic background.”
The paper relies on this without support.
Many uniquely human cognitive and behavioural diseases present polygenic aetiology, making them difficult to study with existing animal models.
“However, many uniquely human cognitive and behavioural diseases — such as autism spectrum disorder (ASD) or schizophrenia — present polygenic aetiology, making them difficult to study with existing animal models.”
The paper relies on this without support.
Many neuropsychiatric diseases involve defects in processes that unfold after birth, such as circuit formation, synaptic pruning, dendritic growth and cortical circuit refinement.
“Many neuropsychiatric diseases manifest defects in processes that unfold postnatally, such as circuit formation, synaptic pruning, dendritic growth and cortical circuit refinement.”
The paper relies on this without support.
Human neuronal networks take years to mature and depend on subcortical influences.
“These neuronal networks can take years to mature in the human brain and rely on subcortical influences”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“they have remained difficult to use to study cortical neuron development in vitro, given the technical challenges of long-term maintenance of functional neurons, whether as monolayer cultures or in organoids”
From Xenotransplanted human cortical neurons reveal species-specific development and functional integration into mouse visual circuits (2019) · cites this paper as Di Lullo and Kriegstein, 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The xenotransplanted neurons also reach much more advanced stages of spine maturation than reported so far in in vitro models of human corticogenesis, using adherent cultures or organoids (Astick and Vanderhaeghen, 2018, Di Lullo and Kriegstein, 2017, Lancaster and Knoblich, 2014)”
From Xenotransplanted human cortical neurons reveal species-specific development and functional integration into mouse visual circuits (2019) · cites this paper as Di Lullo and Kriegstein, 2017
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Consistent with a more mature phenotype, APOE3Ch organoids stained prominently with Reelin, a marker of more mature neurons (Figures 4A–D; Lancaster et al., 2013; Di Lullo and Kriegstein, 2017).”
From APOE3 Christchurch modulates β-catenin/Wnt signaling in iPS cell-derived cerebral organoids from Alzheimer’s cases (2024) · cites this paper as Di Lullo and Kriegstein, 2017
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Human brain organoids are emerging as a scaled-down, three-dimensional model of the human brain, mimicking various developmental features, including generation of new neurons by their conversion from radial glia20 and incorporation into neuronal network21.”
From Therapeutically viable generation of neurons with antisense oligonucleotide suppression of PTB (2021) · cites this paper as [20]
In the citing paper
“Neural organoids present special challenges including a lack of reproducibility, batch-to-batch variation in transcriptional profiles, and susceptibility to small microenvironmental changes that may have a considerable effect on organoid fate165.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [165]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ The use of brain organoids to investigate neural development and disease > Organoids as models of development > Fusing organoids to model complex structures and circuit formation
“Interneuron migration was previously reported in an ‘extrinsic’ cerebral organoid model2; however, the later study exploited the reproducibility afforded by directed differentiation.”
§ The use of brain organoids to investigate neural development and disease > Generating organoids
“Some protocols build on the principles of spontaneous neural induction by using medium that is free of neural induction signalling molecules2,27.”
Citations
Cites
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., et al. (2009) · Nature · doi:10.1038/nature07935 · Cited by 7,204
Cerebral organoids model human brain development and microcephaly
Lancaster, M. A., Renner, M., Martin, C.-A., Wenzel, D., Bicknell, L. S., Hurles, M. E., Homfray, T., Penninger, J. M., Jackson, A. P., & Knoblich, J. A. (2013) · Nature · doi:10.1038/nature12517 · Cited by 5,372
Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling
Chambers, S. M., Fasano, C. A., Papapetrou, E. P., Tomishima, M., Sadelain, M., & Studer, L. (2009) · Nature Biotechnology · doi:10.1038/nbt.1529 · Cited by 3,620
Organoid Models and Applications in Biomedical Research
Xinaris, C., Brizi, V., & Remuzzi, G. (2015) · The Nephron journals/Nephron journals · doi:10.1159/000433566 · Cited by 3,519
Neuropathological alterations in Alzheimer disease
Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006189 · Cited by 3,345
Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure
Qian, X., Nguyen, H. N., Song, M. M., Hadiono, C., Ogden, S. C., Hammack, C., Yao, B., Hamersky, G. R., Jacob, F., Zhong, C., et al. (2016) · Cell · doi:10.1016/j.cell.2016.04.032 · Cited by 2,127
Self-organizing optic-cup morphogenesis in three-dimensional culture
Eiraku, M., Takata, N., Ishibashi, H., Kawada, M., Sakakura, E., Okuda, S., Sekiguchi, K., Adachi, T., & Sasai, Y. (2011) · Nature · doi:10.1038/nature09941 · Cited by 2,001
Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease
Salloway, S., Sperling, R., Fox, N. C., Blennow, K., Klunk, W., Raskind, M., Sabbagh, M., Honig, L. S., Porsteinsson, A. P., Ferris, S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1304839 · Cited by 1,960
Handbook of Experimental Pharmacology.
Meakin, J. W. (1971) · Archives of Internal Medicine · doi:10.1001/archinte.1971.00310230151026 · Cited by 1,959
In vitro differentiation of transplantable neural precursors from human embryonic stem cells
Zhang, S., Wernig, M., Duncan, I. D., Brüstle, O., & Thomson, J. A. (2001) · Nature Biotechnology · doi:10.1038/nbt1201-1129 · Cited by 1,935
Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer's Disease
Doody, R. S., Thomas, R. G., Farlow, M., Iwatsubo, T., Vellas, B., Joffe, S., Kieburtz, K., Raman, R., Sun, X., Aisen, P. S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1312889 · Cited by 1,668
Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture
Paşca, A. M., Sloan, S. A., Clarke, L. E., Tian, Y., Makinson, C. D., Huber, N., Kim, C. H., Park, J.-Y., O'Rourke, N. A., Nguyen, K. D., et al. (2015) · Nature Methods · doi:10.1038/nmeth.3415 · Cited by 1,609
Proneural genes and the specification of neural cell types
Bertrand, N., Castro, D. S., & Guillemot, F. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn874 · Cited by 1,572
Eiraku, M., Watanabe, K., Matsuo-Takasaki, M., Kawada, M., Yonemura, S., Matsumura, M., Wataya, T., Nishiyama, A., Muguruma, K., & Sasai, Y. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.09.002 · Cited by 1,522
Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture
Ying, Q.-L., Stavridis, M., Griffiths, D., Li, M., & Smith, A. (2003) · Nature Biotechnology · doi:10.1038/nbt780 · Cited by 1,504
Regulation of Cerebral Cortical Size by Control of Cell Cycle Exit in Neural Precursors
Chenn, A., & Walsh, C. A. (2002) · Science · doi:10.1126/science.1074192 · Cited by 1,431
Neurogenic radial glia in the outer subventricular zone of human neocortex
Hansen, D. V., Lui, J. H., Parker, P. R. L., & Kriegstein, A. R. (2010) · Nature · doi:10.1038/nature08845 · Cited by 1,388
Self-citationModelling schizophrenia using human induced pluripotent stem cells
Brennand, K. J., Simone, A., Jou, J., Gelboin-Burkhart, C., Tran, N., Sangar, S., Li, Y., Mu, Y., Chen, G., Yu, D., et al. (2011) · Nature · doi:10.1038/nature09915 · Cited by 1,375
Assembly of functionally integrated human forebrain spheroids
Birey, F., Andersen, J., Makinson, C. D., Islam, S., Wei, W., Huber, N., Fan, H. C., Metzler, K. R. C., Panagiotakos, G., Thom, N., et al. (2017) · Nature · doi:10.1038/nature22330 · Cited by 1,365
Development and Evolution of the Human Neocortex
Lui, J. H., Hansen, D. V., & Kriegstein, A. R. (2011) · Cell · doi:10.1016/j.cell.2011.06.030 · Cited by 1,342
Self-citationMarchetto, M. C. N., Carromeu, C., Acab, A., Yu, D., Yeo, G. W., Mu, Y., Chen, G., Gage, F. H., & Muotri, A. R. (2010) · Cell · doi:10.1016/j.cell.2010.10.016 · Cited by 1,329
The Brazilian Zika virus strain causes birth defects in experimental models
Cugola, F. R., Fernandes, I. R., Russo, F. B., Freitas, B. C., Dias, J. L. M., Guimarães, K. P., Benazzato, C., Almeida, N., Pignatari, G. C., Romero, S., et al. (2016) · Nature · doi:10.1038/nature18296 · Cited by 1,326
Cell diversity and network dynamics in photosensitive human brain organoids
Quadrato, G., Nguyen, T., Macosko, E. Z., Sherwood, J. L., Min Yang, S., Berger, D. R., Maria, N., Scholvin, J., Goldman, M., Kinney, J. P., et al. (2017) · Nature · doi:10.1038/nature22047 · Cited by 1,321
Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth
Tang, H., Hammack, C., Ogden, S. C., Wen, Z., Qian, X., Li, Y., Yao, B., Shin, J., Zhang, F., Lee, E. M., et al. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.02.016 · Cited by 1,292
A Phase 3 Trial of Semagacestat for Treatment of Alzheimer's Disease
Doody, R. S., Raman, R., Farlow, M., Iwatsubo, T., Vellas, B., Joffe, S., Kieburtz, K., He, F., Sun, X., Thomas, R. G., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1210951 · Cited by 1,224
A three-dimensional human neural cell culture model of Alzheimer’s disease
Choi, S. H., Kim, Y. H., Hebisch, M., Sliwinski, C., Lee, S., D’Avanzo, C., Chen, H., Hooli, B., Asselin, C., Muffat, J., et al. (2014) · Nature · doi:10.1038/nature13800 · Cited by 1,195
Zika virus impairs growth in human neurospheres and brain organoids
Garcez, P. P., Loiola, E. C., Madeiro da Costa, R., Higa, L. M., Trindade, P., Delvecchio, R., Nascimento, J. M., Brindeiro, R., Tanuri, A., & Rehen, S. K. (2016) · Science · doi:10.1126/science.aaf6116 · Cited by 1,184
FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders
Mariani, J., Coppola, G., Zhang, P., Abyzov, A., Provini, L., Tomasini, L., Amenduni, M., Szekely, A., Palejev, D., Wilson, M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.06.034 · Cited by 1,149
Human cerebral organoids recapitulate gene expression programs of fetal neocortex development
Camp, J. G., Badsha, F., Florio, M., Kanton, S., Gerber, T., Wilsch-Bräuninger, M., Lewitus, E., Sykes, A., Hevers, W., Lancaster, M., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520760112 · Cited by 1,130
Kadoshima, T., Sakaguchi, H., Nakano, T., Soen, M., Ando, S., Eiraku, M., & Sasai, Y. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1315710110 · Cited by 999
Microglia Regulate the Number of Neural Precursor Cells in the Developing Cerebral Cortex
Cunningham, C. L., Martínez-Cerdeño, V., & Noctor, S. C. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3441-12.2013 · Cited by 976
Shi, Y., Kirwan, P., & Livesey, F. J. (2012) · Nature Protocols · doi:10.1038/nprot.2012.116 · Cited by 972
Molecular Identity of Human Outer Radial Glia during Cortical Development
Pollen, A. A., Nowakowski, T. J., Chen, J., Retallack, H., Sandoval-Espinosa, C., Nicholas, C. R., Shuga, J., Liu, S. J., Oldham, M. C., Diaz, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.09.004 · Cited by 908
Self-citationJo, J., Xiao, Y., Sun, A. X., Cukuroglu, E., Tran, H.-D., Göke, J., Tan, Z. Y., Saw, T. Y., Tan, C.-P., Lokman, H., et al. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.07.005 · Cited by 861
OSVZ progenitors of human and ferret neocortex are epithelial-like and expand by integrin signaling
Fietz, S. A., Kelava, I., Vogt, J., Wilsch-Bräuninger, M., Stenzel, D., Fish, J. L., Corbeil, D., Riehn, A., Distler, W., Nitsch, R., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2553 · Cited by 830
Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses
Shi, Y., Kirwan, P., Smith, J., Robinson, H. P. C., & Livesey, F. J. (2012) · Nature Neuroscience · doi:10.1038/nn.3041 · Cited by 813
Fused cerebral organoids model interactions between brain regions
Bagley, J. A., Reumann, D., Bian, S., Lévi-Strauss, J., & Knoblich, J. A. (2017) · Nature Methods · doi:10.1038/nmeth.4304 · Cited by 790
Directed differentiation of telencephalic precursors from embryonic stem cells
Watanabe, K., Kamiya, D., Nishiyama, A., Katayama, T., Nozaki, S., Kawasaki, H., Watanabe, Y., Mizuseki, K., & Sasai, Y. (2005) · Nature Neuroscience · doi:10.1038/nn1402 · Cited by 784
Dang, J., Tiwari, S. K., Lichinchi, G., Qin, Y., Patil, V. S., Eroshkin, A. M., & Rana, T. M. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.04.014 · Cited by 731
Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development
Furuta, Y., Piston, D. W., & Hogan, B. L. M. (1997) · Development · doi:10.1242/dev.124.11.2203 · Cited by 710
Self-Organization of Polarized Cerebellar Tissue in 3D Culture of Human Pluripotent Stem Cells
Muguruma, K., Nishiyama, A., Kawakami, H., Hashimoto, K., & Sasai, Y. (2015) · Cell Reports · doi:10.1016/j.celrep.2014.12.051 · Cited by 692
Smart, I. H. M. (2002) · Cerebral Cortex · doi:10.1093/cercor/12.1.37 · Cited by 687
Kirkeby, A., Grealish, S., Wolf, D. A., Nelander, J., Wood, J., Lundblad, M., Lindvall, O., & Parmar, M. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.04.009 · Cited by 662
The Role of Glia in the Spinal Cord in Neuropathic and Inflammatory Pain
Old, E. A., Clark, A. K., & Malcangio, M. (2015) · Handbook of experimental pharmacology · doi:10.1007/978-3-662-46450-2_8 · Cited by 662
Cell-cycle control and cortical development
Dehay, C., & Kennedy, H. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2097 · Cited by 655
An intrinsic mechanism of corticogenesis from embryonic stem cells
Gaspard, N., Bouschet, T., Hourez, R., Dimidschstein, J., Naeije, G., van den Ameele, J., Espuny-Camacho, I., Herpoel, A., Passante, L., Schiffmann, S. N., et al. (2008) · Nature · doi:10.1038/nature07287 · Cited by 641
Grove, E. A., Tole, S., Limon, J., Yip, L., & Ragsdale, C. W. (1998) · Development · doi:10.1242/dev.125.12.2315 · Cited by 587
Raja, W. K., Mungenast, A. E., Lin, Y.-T., Ko, T., Abdurrob, F., Seo, J., & Tsai, L.-H. (2016) · PLOS ONE · doi:10.1371/journal.pone.0161969 · Cited by 569
Bershteyn, M., Nowakowski, T. J., Pollen, A. A., Di Lullo, E., Nene, A., Wynshaw-Boris, A., & Kriegstein, A. R. (2017) · Cell Stem Cell · doi:10.1016/j.stem.2016.12.007 · Cited by 566
Self-citationDifferential responses to lithium in hyperexcitable neurons from patients with bipolar disorder
Study, T. P. O. B. D., Mertens, J., Wang, Q.-W., Kim, Y., Yu, D. X., Pham, S., Yang, B., Zheng, Y., Diffenderfer, K. E., Zhang, J., et al. (2015) · Nature · doi:10.1038/nature15526 · Cited by 562
Sakaguchi, H., Kadoshima, T., Soen, M., Narii, N., Ishida, Y., Ohgushi, M., Takahashi, J., Eiraku, M., & Sasai, Y. (2015) · Nature Communications · doi:10.1038/ncomms9896 · Cited by 542
Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells
Nowakowski, T. J., Pollen, A. A., Di Lullo, E., Sandoval-Espinosa, C., Bershteyn, M., & Kriegstein, A. R. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.03.012 · Cited by 529
Self-citationA new subtype of progenitor cell in the mouse embryonic neocortex
Wang, X., Tsai, J.-W., LaMonica, B., & Kriegstein, A. R. (2011) · Nature Neuroscience · doi:10.1038/nn.2807 · Cited by 507
Self-citationZika virus cell tropism in the developing human brain and inhibition by azithromycin
Retallack, H., Di Lullo, E., Arias, C., Knopp, K. A., Laurie, M. T., Sandoval-Espinosa, C., Mancia Leon, W. R., Krencik, R., Ullian, E. M., Spatazza, J., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1618029113 · Cited by 506
Self-citationInduced Pluripotent Stem Cells Meet Genome Editing
Hockemeyer, D., & Jaenisch, R. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.04.013 · Cited by 499
Self-formation of functional adenohypophysis in three-dimensional culture
Suga, H., Kadoshima, T., Minaguchi, M., Ohgushi, M., Soen, M., Nakano, T., Takata, N., Wataya, T., Muguruma, K., Miyoshi, H., et al. (2011) · Nature · doi:10.1038/nature10637 · Cited by 497
Wnt Signaling Mediates Self-Organization and Axis Formation in Embryoid Bodies
ten Berge, D., Koole, W., Fuerer, C., Fish, M., Eroglu, E., & Nusse, R. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.09.013 · Cited by 477
Axl Mediates ZIKA Virus Entry in Human Glial Cells and Modulates Innate Immune Responses
Meertens, L., Labeau, A., Dejarnac, O., Cipriani, S., Sinigaglia, L., Bonnet-Madin, L., Le Charpentier, T., Hafirassou, M. L., Zamborlini, A., Cao-Lormeau, V.-M., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.12.045 · Cited by 450
Induction of Expansion and Folding in Human Cerebral Organoids
Li, Y., Muffat, J., Omer, A., Bosch, I., Lancaster, M. A., Sur, M., Gehrke, L., Knoblich, J. A., & Jaenisch, R. (2017) · Cell Stem Cell · doi:10.1016/j.stem.2016.11.017 · Cited by 436
Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells
Monzel, A. S., Smits, L. M., Hemmer, K., Hachi, S., Moreno, E. L., van Wuellen, T., Jarazo, J., Walter, J., Brüggemann, I., Boussaad, I., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.03.010 · Cited by 435
Self‐organized developmental patterning and differentiation in cerebral organoids
Renner, M., Lancaster, M. A., Bian, S., Choi, H., Ku, T., Peer, A., Chung, K., & Knoblich, J. A. (2017) · The EMBO Journal · doi:10.15252/embj.201694700 · Cited by 389
Generating Neuronal Diversity in the Mammalian Cerebral Cortex
Lodato, S., & Arlotta, P. (2015) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100814-125353 · Cited by 389
Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain
Luo, C., Lancaster, M. A., Castanon, R., Nery, J. R., Knoblich, J. A., & Ecker, J. R. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.12.001 · Cited by 370
Nowakowski, T. J., Pollen, A. A., Sandoval-Espinosa, C., & Kriegstein, A. R. (2016) · Neuron · doi:10.1016/j.neuron.2016.09.005 · Cited by 362
Self-citationOtani, T., Marchetto, M. C., Gage, F. H., Simons, B. D., & Livesey, F. J. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.03.003 · Cited by 353
G1 Phase Regulation, Area-Specific Cell Cycle Control, and Cytoarchitectonics in the Primate Cortex
Lukaszewicz, A., Savatier, P., Cortay, V., Giroud, P., Huissoud, C., Berland, M., Kennedy, H., & Dehay, C. (2005) · Neuron · doi:10.1016/j.neuron.2005.06.032 · Cited by 315
The promises and challenges of human brain organoids as models of neuropsychiatric disease
Quadrato, G., Brown, J., & Arlotta, P. (2016) · Nature Medicine · doi:10.1038/nm.4214 · Cited by 304
Making bigger brains–the evolution of neural-progenitor-cell division
Fish, J. L., Dehay, C., Kennedy, H., & Huttner, W. B. (2008) · Journal of Cell Science · doi:10.1242/jcs.023465 · Cited by 274
Wells, M. F., Salick, M. R., Wiskow, O., Ho, D. J., Worringer, K. A., Ihry, R. J., Kommineni, S., Bilican, B., Klim, J. R., Hill, E. J., et al. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.11.011 · Cited by 269
Contributions of cortical subventricular zone to the development of the human cerebral cortex
Zecevic, N., Chen, Y., & Filipovic, R. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20714 · Cited by 269
Iefremova, V., Manikakis, G., Krefft, O., Jabali, A., Weynans, K., Wilkens, R., Marsoner, F., Brändl, B., Müller, F.-J., Koch, P., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.03.047 · Cited by 261
Effects of canonical Wnt signaling on dorso-ventral specification of the mouse telencephalon.
Backman, M., Machoň, O., Mygland, L., van den Bout, C. J., Zhong, W., Taketo, M., & Krauss, S. (2005) · Developmental Biology · doi:10.1016/j.ydbio.2004.12.010 · Cited by 243
Machoň, O., Backman, M., Machoňová, O., Kozmík, Z., Vacı́k, T., Andersen, L., & Krauss, S. J. K. (2007) · Developmental Biology · doi:10.1016/j.ydbio.2007.08.038 · Cited by 219
Diseases in a dish: modeling human genetic disorders using induced pluripotent cells
Tiscórnia, G., Lorenzo-Vivas, E., & Belmonte, J. C. I. (2011) · Nature Medicine · doi:10.1038/nm.2504 · Cited by 211
Martínez-Cerdeño, V., Cunningham, C. L., Camacho, J., Antczak, J. L., Prakash, A. N., Cziep, M. E., Walker, A. I., & Noctor, S. C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030178 · Cited by 203
Wnt Signaling in Vertebrate Axis SpecificationPreprint
Hikasa, H., & Sokol, S. Y. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a007955 · Cited by 178
Madison, J. M., Zhou, F., Nigam, A., Hussain, A. H., Barker, D., Nehme, R., van der Ven, K., Hsu, J. Y., Wolf, P., Fleishman, M., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.7 · Cited by 177
Wnt Signaling and Forebrain DevelopmentPreprint
Harrison-Uy, S. J., & Pleasure, S. J. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008094 · Cited by 168
A Stem Cell Niche for Intermediate Progenitor Cells of the Embryonic Cortex
Javaherian, A., & Kriegstein, A. (2009) · Cerebral Cortex · doi:10.1093/cercor/bhp029 · Cited by 155
Self-citationLindborg, B. A., Brekke, J. H., Vegoe, A. L., Ulrich, C. B., Haider, K. T., Subramaniam, S., Venhuizen, S. L., Eide, C. R., Orchard, P. J., Chen, W., et al. (2016) · Stem Cells Translational Medicine · doi:10.5966/sctm.2015-0305 · Cited by 141
Neurovascular Congruence during Cerebral Cortical Development
Stubbs, D., DeProto, J., Nie, K., Englund, C., Mahmud, I., Hevner, R., & Molnár, Z. (2009) · Cerebral Cortex · doi:10.1093/cercor/bhp040 · Cited by 133
Is this a brain which I see before me? Modeling human neural development with pluripotent stem cells
Suzuki, I. K., & Vanderhaeghen, P. (2015) · Development · doi:10.1242/dev.120568 · Cited by 110
Decision making during interneuron migration in the developing cerebral cortex
Guo, J., & Anton, E. S. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.12.001 · Cited by 104
Edri, R., Yaffe, Y., Ziller, M. J., Mutukula, N., Volkman, R., David, E., Jacob‐Hirsch, J., Malcov, H., Levy, C., Rechavi, G., et al. (2015) · Nature Communications · doi:10.1038/ncomms7500 · Cited by 98
The cortical hem regulates the size and patterning of neocortex
Caronia, G., Yoshida, M., Gulden, F. O., Assimacopoulos, S., & Grove, E. A. (2014) · Development · doi:10.1242/dev.106914 · Cited by 96
Nasu, M., Takata, N., Danjo, T., Sakaguchi, H., Kadoshima, T., Futaki, S., Sekiguchi, K., Eiraku, M., & Sasai, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0053024 · Cited by 94
Modeling psychiatric disorders with patient-derived iPSCs
Wen, Z., Christian, K. M., Song, H., & Ming, G.-L. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2015.11.003 · Cited by 84
Voronova, A., Yuzwa, S. A., Wang, B. S., Zahr, S. K., Syal, C., Wang, J., Kaplan, D. R., & Miller, F. D. (2017) · Neuron · doi:10.1016/j.neuron.2017.04.018 · Cited by 78
Weitzer, G. (2006) · Handbook of experimental pharmacology · doi:10.1007/3-540-31265-x_2 · Cited by 66
oRGs and mitotic somal translocation — a role in development and disease
Ostrem, B., Di Lullo, E., & Kriegstein, A. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2016.11.007 · Cited by 61
Self-citationMechanisms Underlying the Specification, Positional Regulation, and Function of the Cortical Hem
Subramanian, L., & Tole, S. (2009) · Cerebral Cortex · doi:10.1093/cercor/bhp031 · Cited by 52
Genome engineering of stem cell organoids for disease modeling
Sun, Y., & Ding, Q. (2017) · Protein & Cell · doi:10.1007/s13238-016-0368-0 · Cited by 39
Flaherty, E. K., & Brennand, K. J. (2017) · Brain Research · doi:10.1016/j.brainres.2015.11.009 · Cited by 19
Cited by
Sorted by citations
An in vivo model of functional and vascularized human brain organoids
Mansour, A. A., Gonçalves, J. T., Bloyd, C. W., Li, H., Fernandes, S., Quang, D., Johnston, S., Parylak, S. L., Jin, X., & Gage, F. H. (2018) · Nature Biotechnology · doi:10.1038/nbt.4127 · Cited by 1,211
Hofer, M., & Lutolf, M. P. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00279-y · Cited by 1,184
Reliability of human cortical organoid generation
Yoon, S.-J., Elahi, L. S., Pașca, A. M., Marton, R. M., Gordon, A., Revah, O., Miura, Y., Walczak, E. M., Holdgate, G. M., Fan, H. C., et al. (2019) · Nature Methods · doi:10.1038/s41592-018-0255-0 · Cited by 507
Generation and assembly of human brain region-specific three-dimensional cultures
Sloan, S. A., Andersen, J., Pașca, A. M., Birey, F., & Pașca, S. P. (2018) · Nature Protocols · doi:10.1038/s41596-018-0032-7 · Cited by 490
Modeling Alzheimer’s disease with iPSC-derived brain cells
Penney, J., Ralvenius, W. T., & Tsai, L.-H. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0468-3 · Cited by 471
Metadata
- Authors
- Di Lullo, E., & Kriegstein, A. R.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Kriegstein, Arnold R.
- Venue
- Nature Reviews Neuroscience
- Published
- 2017-09-07
- Volume
- 18
- Issue
- 10
- Pages
- 573-584
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- PMC
- PMC5667942
- OpenAlex
- W2753168648
- Cited by
- 788
- References
- 94
- Citations by year
- 2026: 60 · 2025: 95 · 2024: 122 · 2023: 84 · 2022: 100 · 2021: 100 · 2020: 101 · 2019: 70 · 2018: 53 · 2017: 2
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R35NS097305)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- brain organoids, neural development, human brain development, pluripotent stem cells, organoid formation, brain disease model, in vitro brain models
- MeSH terms
- Animals, Brain, Brain Diseases, Humans, Models, Neurological, Organoids, Pluripotent Stem Cells, Neurogenesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-01, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-01 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
