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Cerebral organoids model human brain development and microcephaly
Open accessAbstract
The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development. Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype. Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissue.
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“With their 3D structures and cell components resembling the human brain, these organoids can replicate the complex brain microenvironment better than 2D in vitro models (15–17, 19)”
From Understanding monocyte-driven neuroinflammation in Alzheimer’s disease using human cortical organoid microphysiological systems (2025) · cites this paper as [15]
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.
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“hiPSC-derived astrocytes, which can be generated with a fast protocol in 2D layers104 or integrated in 3D systems such as spheroids and organoids105–108”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [106]
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 differentiation protocol was further optimized by integrating established principles of neuronal development to ensure reproducibility and high neuronal purity (Lancaster et al. 2013;Lancaster and Knoblich 2014a;Lancaster and Knoblich 2014b).”
From TMEM55B downregulation promotes neurodegeneration in Alzheimer’s disease models (2026) · cites this paper as Lancaster et al. 2013
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Promising disease models of the liver65,66, pancreas67,68, central nervous system35,69,70, skin71, lung72,73, intestine72–76, musculoskeletal system77 and heart78–81 have been developed, but their equivalence or superiority over their animal models needs to be demonstrated.”
From Human disease models in drug development (2023) · cites this paper as [35]
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In the citing paper
“Apart from growth factor cues, other modulators — such as scaffold support provided by the extracellular matrix — are important features of current protocols2,5,28.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [2]
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In the citing paper
“These 3D “organoids” are often found to have instructive morphogenetic cues resulting in self organization similarly found in vivo [53,54].”
From Utility of iPSC-Derived Cells for Disease Modeling, Drug Development, and Cell Therapy (2022) · cites this paper as [53]
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In the citing paper
“Human brain organoids are 3D cultures derived from human pluripotent stem cells and recapitulate native brain cellular components, cytoarchitecture, and exhibit neural activity.22–24”
From Tubular human brain organoids to model microglia-mediated neuroinflammation (2021) · cites this paper as [22]
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In the citing paper
“Organoid development followed the expected temporal changes (Lancaster et al., 2013; Velasco et al., 2019; Watanabe et al., 2017; Yoon et al., 2019; Figures 1B–1D; Figure S1A).”
From ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids (2021) · cites this paper as Lancaster et al., 2013
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In the citing paper
“Although organoids have been used to investigate disease-associated genes9–11, they are limited by phenotypic variability and low throughput.”
From Single-cell brain organoid screening identifies developmental defects in autism (2023) · cites this paper as [9]
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In the citing paper
“Brain organoids recapitulate early brain development and generate diverse cell types found in vivo9.”
From Single-cell brain organoid screening identifies developmental defects in autism (2023) · cites this paper as [9]
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 Lancaster et al., 2013
In the citing 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.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [2]
In the citing paper
“Both of these protocols generated organoids containing a dorsalized neuroepithelium that reproduced certain aspects of cortical development, both structurally and in terms of cell behaviour.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [2]
In the citing 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.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [2]
In the citing 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).”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [2]
In the citing paper
“Cerebral organoids grown from these cells contained fewer proliferating progenitor cells and showed premature neural differentiation compared to wild-type counterparts.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [2]
In the citing 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.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [2]
In the citing paper
“Intriguingly, UBA1 is widely expressed in the human body, but loss-of-function mutations are linked to neurodegenerative diseases110.”
From CRISPR-based functional genomics for neurological disease (2020) · cites this paper as [110]
In the citing paper
“Cerebral or other unguided neural organoids develop from embryonic stem (ES) cells or induced pluripotent stem (iPS) cells into a three-dimensional neuroepithelium that self-patterns, regionalizes and, ultimately, forms neurons of the different brain regions1–3.”
From Inferring and perturbing cell fate regulomes in human brain organoids (2023) · cites this paper as [2]
In the citing paper
“Self-organizing neural organoids grown from pluripotent stem cells1–3 combined with single-cell genomic technologies provide opportunities to examine gene regulatory networks underlying human brain development.”
From Inferring and perturbing cell fate regulomes in human brain organoids (2023) · cites this paper as [2]
In the citing paper
“Brain organoids have been used to successfully model microcephaly2, periventricular heterotopia10, autism11 and other neurodevelopmental disorders12,13 that may have differential effects on the various human brain regions.”
From Inferring and perturbing cell fate regulomes in human brain organoids (2023) · cites this paper as [2]
In the citing paper
“IPSC models of rare microcephaly syndromes have been shown to undergo loss of neuronal progenitor cells and premature neural differentiation (Lancaster et al., 2013).”
From Getting to the cores of autism (2019) · cites this paper as Lancaster et al., 2013
In the citing paper
“Three-dimensional brain organoids derived from human pluripotent stem cells (hPSCs) have shown significant advantages in modeling neurological disorders including autism, microcephaly and Parkinson’s disease.528–530”
From Amyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future (2023) · cites this paper as [528]
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Citations
Cites
Takahashi, K., & Yamanaka, S. (2006) · Cell · doi:10.1016/j.cell.2006.07.024 · Cited by 26,673
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
Generation of germline-competent induced pluripotent stem cells
Okita, K., Ichisaka, T., & Yamanaka, S. (2007) · Nature · doi:10.1038/nature05934 · Cited by 4,408
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
The cell biology of neurogenesis
Götz, M., & Huttner, W. B. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1739 · Cited by 2,130
A ROCK inhibitor permits survival of dissociated human embryonic stem cells
Watanabe, K., Ueno, M., Kamiya, D., Nishiyama, A., Matsumura, M., Wataya, T., Takahashi, J. B., Nishikawa, S., Nishikawa, S.-I., Muguruma, K., et al. (2007) · Nature Biotechnology · doi:10.1038/nbt1310 · Cited by 2,055
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
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
Self-formation of optic cups and storable stratified neural retina from human ESCs
Nakano, T., Ando, S., Takata, N., Kawada, M., Muguruma, K., Sekiguchi, K., Saito, K., Yonemura, S., Eiraku, M., & Sasai, Y. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.05.009 · Cited by 1,447
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
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Wang, M., Zhang, L., & Gage, F. H. (2019) · Protein & Cell · doi:10.1007/s13238-019-0638-8 · Cited by 76
Modeling human embryo development with embryonic and extra-embryonic stem cells
Weatherbee, B. A. T., Cui, T., & Zernicka‐Goetz, M. (2020) · Developmental Biology · doi:10.1016/j.ydbio.2020.12.010 · Cited by 79
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Fritsche, E., Haarmann‐Stemmann, T., Kapr, J., Galanjuk, S., Hartmann, J., Mertens, P. R., Kämpfer, A. A. M., Schins, R. P. F., Tigges, J., & Koch, K. (2020) · Small · doi:10.1002/smll.202006252 · Cited by 78
Advances in development and application of human organoids
Shankaran, A., Prasad, K., Chaudhari, S., Brand, A. M., & Satyamoorthy, K. (2021) · 3 Biotech · doi:10.1007/s13205-021-02815-7 · Cited by 77
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Paolillo, M., Comincini, S., & Schinelli, S. (2021) · Cancers · doi:10.3390/cancers13102449 · Cited by 84
Folding brains: from development to disease modeling
Del-Valle-Anton, L., & Borrell, V. (2021) · Physiological Reviews · doi:10.1152/physrev.00016.2021 · Cited by 79
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Arias, A. M., Marikawa, Y., & Moris, N. (2022) · Developmental Biology · doi:10.1016/j.ydbio.2022.05.002 · Cited by 76
Váňová, T., Sedmík, J., Raška, J., Černá, K. A., Tauš, P., Pospisilova, V., Nezvedová, M., Fedorová, V., Kadakova, S., Klímová, H., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113310 · Cited by 81
Wang, M., Zhang, L., Novak, S. W., Yu, J., Gallina, I. S., Xu, L. L., Lim, C. K., Fernandes, S., Shokhirev, M. N., Williams, A. E., et al. (2024) · Nature Biotechnology · doi:10.1038/s41587-024-02157-8 · Cited by 78
Six-month cultured cerebral organoids from human ES cells contain matured neural cells
Matsui, T. K., Matsubayashi, M., Sakaguchi, Y. M., Hayashi, R. K., Zheng, C., Sugie, K., Hasegawa, M., Nakagawa, T., & Mori, E. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.01.040 · Cited by 80
Roccio, M., & Edge, A. S. B. (2019) · Development · doi:10.1242/dev.177188 · Cited by 76
Organoid technology for tissue engineering
He, J., Zhang, X., Xia, X., Han, M., Li, F., Li, C., Li, Y., & Gao, D. (2020) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjaa012 · Cited by 78
Ruiz-Garcia, H. J., Alvarado-Estrada, K., Schiapparelli, P. V., Quiñones‐Hinojosa, A., & Trifiletti, D. M. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.558381 · Cited by 76
Múnera, J. O., Kechele, D. O., Bouffi, C., Qu, N., Jing, R., Maity, P. P., Enriquez, J. R., Han, L., Campbell, I., Mahé, M. M., et al. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.10.002 · Cited by 74
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Rauner, G., Gupta, P. B., & Kuperwasser, C. (2025) · Nature Methods · doi:10.1038/s41592-025-02769-1 · Cited by 82
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Wang, N., Zhang, H., Zhang, B., Liu, W., Zhang, Z., Qiao, M., Zhang, H., Deng, F., Wu, N., Chen, X., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093608 · Cited by 74
Watson, P. M. D., Kavanagh, E., Allenby, G., & Vassey, M. (2017) · SLAS Discovery · doi:10.1177/2472555217691450 · Cited by 74
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Janssens, S., Schotsaert, M., Karnik, R., Balasubramaniam, V. R. M. T., Déjosez, M., Meissner, A., García‐Sastre, A., & Zwaka, T. P. (2018) · mSystems · doi:10.1128/msystems.00219-17 · Cited by 75
Consent for governance in the ethical use of organoids
Boers, S. N., & Bredenoord, A. L. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0112-5 · Cited by 80
Human cerebral organoids as a therapeutic drug screening model for Creutzfeldt–Jakob disease
Groveman, B. R., Ferreira, N., Foliaki, S. T., Walters, R. O., Winkler, C. W., Race, B., Hughson, A. G., Zanusso, G., & Haigh, C. L. (2021) · Scientific Reports · doi:10.1038/s41598-021-84689-6 · Cited by 76
Optogenetic control of apical constriction induces synthetic morphogenesis in mammalian tissues
Martínez-Ara, G., Taberner, N., Takayama, M., Sandaltzopoulou, E., Villava, C. E., Bosch-Padrós, M., Takata, N., Trepat, X., Eiraku, M., & Ebisuya, M. (2022) · Nature Communications · doi:10.1038/s41467-022-33115-0 · Cited by 73
Morphodynamics of human early brain organoid development
Jain, A., Gut, G., Sanchis-Calleja, F., Tschannen, R., He, Z., Luginbühl, N., Zenk, F., Chrisnandy, A., Streib, S., Harmel, C., et al. (2025) · Nature · doi:10.1038/s41586-025-09151-3 · Cited by 73
Pseudostratified epithelia – cell biology, diversity and roles in organ formation at a glance
Norden, C. (2017) · Journal of Cell Science · doi:10.1242/jcs.192997 · Cited by 73
Biomimicry, Biofabrication, and Biohybrid Systems: The Emergence and Evolution of Biological Design
Raman, R., & Bashir, R. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201700496 · Cited by 76
Next-Generation Liver Medicine Using Organoid Models
Akbari, S., Arslan, N., Senturk, S., & Erdal, E. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00345 · Cited by 72
Recapitulating Cell–Cell Interactions for Organoid Construction – Are Biomaterials Dispensable?
Wan, A. C. A. (2016) · Trends in biotechnology · doi:10.1016/j.tibtech.2016.02.015 · Cited by 72
Biology Explaining Tooth Repair and Regeneration: A Mini-Review
Balic, A. (2018) · Gerontology · doi:10.1159/000486592 · Cited by 72
Organoid technology in cancer precision medicine
Xia, X., Li, F., He, J., Aji, R., & Gao, D. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.04.039 · Cited by 72
Qiao, H., Guo, M., Shang, J., Zhao, W., Wang, Z., Liu, N., Li, B., Zhou, Y., Wu, Y., & Chen, P. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1008899 · Cited by 72
Towards manufacturing of human organoids
Ashok, A., Choudhury, D., Fang, Y., & Hunziker, W. (2019) · Biotechnology Advances · doi:10.1016/j.biotechadv.2019.107460 · Cited by 73
Recent advances in gene therapy for neurodevelopmental disorders with epilepsy
Turner, T. J., Zourray, C., Schorge, S., & Lignani, G. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15168 · Cited by 71
Mazzola, M., & Pasquale, E. D. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00455 · Cited by 71
Dissecting the Genetic and Etiological Causes of Primary Microcephaly
Jean, F., Stuart, A., & Tarailo‐Graovac, M. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.570830 · Cited by 72
Scalise, M., Marino, F., Salerno, L., Cianflone, E., Molinaro, C., Salerno, N., Angelis, A. D., Viglietto, G., Urbanek, K., & Torella, D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413180 · Cited by 68
Optimizing neuronal differentiation from induced pluripotent stem cells to model ASD
Kim, D.-S., Ross, P. J., Zaslavsky, K., & Ellis, J. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00109 · Cited by 70
Zhang, Y. S., & Khademhosseini, A. (2015) · Nanomedicine · doi:10.2217/nnm.15.18 · Cited by 71
hPSC-derived lung and intestinal organoids as models of human fetal tissue
Aurora, M., & Spence, J. R. (2016) · Developmental Biology · doi:10.1016/j.ydbio.2016.06.006 · Cited by 69
Complexity of the Wnt/β‑catenin pathway: Searching for an activation model
Tortelote, G. G., dos Reis, R. R., Mendes, F. A., & Abreu, J. G. (2017) · Cellular Signalling · doi:10.1016/j.cellsig.2017.08.008 · Cited by 71
Human Cytomegalovirus Compromises Development of Cerebral Organoids
Brown, R. M., Rana, P. S. J. B., Jaeger, H. K., O’Dowd, J. M., Balemba, O. B., & Fortunato, E. A. (2019) · Journal of Virology · doi:10.1128/jvi.00957-19 · Cited by 70
Towards Advanced iPSC-based Drug Development for Neurodegenerative Disease
Pasteuning-Vuhman, S., de Jongh, R., Timmers, A., & Pasterkamp, R. J. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.09.013 · Cited by 72
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Hoang, P., & Ma, Z. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.01.026 · Cited by 71
Recent Advances in Three-Dimensional Stem Cell Culture Systems and Applications
Wu, X., Su, J., Wei, J., Jiang, N., & Ge, X. (2021) · Stem Cells International · doi:10.1155/2021/9477332 · Cited by 72
Advances in ex vivo models and lab-on-a-chip devices for neural tissue engineering
Mobini, S., Song, Y. H., McCrary, M. W., & Schmidt, C. E. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.05.012 · Cited by 72
Sood, D., Cairns, D. M., Dabbi, J. M., Ramakrishnan, C., Deisseroth, K. A., Black, L. D., Santaniello, S., & Kaplan, D. L. (2019) · Scientific Reports · doi:10.1038/s41598-019-54248-1 · Cited by 72
To Simulate or Not to Simulate: What Are the Questions?
Dudai, Y., & Evers, K. (2014) · Neuron · doi:10.1016/j.neuron.2014.09.031 · Cited by 68
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Knowlton, S. M., Cho, Y. K., Li, X. J., Khademhosseini, A., & Taşoğlu, S. (2016) · Biomaterials Science · doi:10.1039/c5bm00324e · Cited by 69
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Lin, A., Skottvoll, F. S., Rayner, S., Pedersen‐Bjergaard, S., Sullivan, G. J., Krauss, S. J. K., Wilson, S. R., & Harrison, S. P. (2019) · Electrophoresis · doi:10.1002/elps.201900170 · Cited by 72
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Shariati, L., Esmaeili, Y., Javanmard, S. H., Bidram, E., & Amini, A. (2021) · Stem Cells · doi:10.1002/stem.3379 · Cited by 71
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Tayler, I. M., & Stowers, R. S. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.04.020 · Cited by 70
Fu, Q., Qin, Z., Jin, X., Zhang, L., Chen, Z., He, J., Ji, J., & Yao, K. (2017) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.16-20504 · Cited by 69
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Ekert, J. E., Deakyne, J., Pribul-Allen, P., Terry, R., Schofield, C., Jeong, C. G., Storey, J., Mohamet, L., Francis, J., Naidoo, A., et al. (2020) · SLAS DISCOVERY · doi:10.1177/2472555220923332 · Cited by 68
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Teriyapirom, I., Batista-Rocha, A. S., & Koo, B.-K. (2021) · Journal of Molecular Medicine · doi:10.1007/s00109-020-02029-z · Cited by 68
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Picollet-D’hahan, N., Dolega, M. E., Liguori, L., Marquette, C., Le Gac, S., Gidrol, X., & Martin, D. K. (2016) · Trends in Biotechnology · doi:10.1016/j.tibtech.2016.06.012 · Cited by 65
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Jensen, G., Morrill, C. C., & Huang, Y. (2018) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2018.03.006 · Cited by 68
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Wiegand, C., & Banerjee, I. (2019) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2019.05.011 · Cited by 69
CSS: cluster similarity spectrum integration of single-cell genomics data
He, Z., Brazovskaja, A., Ebert, S., Camp, J. G., & Treutlein, B. (2020) · Genome biology · doi:10.1186/s13059-020-02147-4 · Cited by 63
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Liu, C., Fu, Z., Wu, S., Wang, X., Zhang, S., Chu, C., Hong, Y., Wu, W., Chen, S., Jiang, Y., et al. (2022) · EMBO Molecular Medicine · doi:10.15252/emmm.202215851 · Cited by 70
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Yin, J., & Schaaf, C. P. (2016) · Prenatal Diagnosis · doi:10.1002/pd.4942 · Cited by 78
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Park, G.-S., Park, M. H., Shin, W., Zhao, C., Sheikh, S., Oh, S. J., & Kim, H. J. (2017) · Stem Cell Reviews and Reports · doi:10.1007/s12015-017-9739-z · Cited by 71
Harberts, J. I., Fendler, C., Teuber, J., Siegmund, M., Trenkle, A. D. S., Rieck, N., Wolpert, M., Zierold, R., & Blick, R. H. (2020) · ACS Nano · doi:10.1021/acsnano.0c04640 · Cited by 68
Genome Editing in iPSC-Based Neural Systems: From Disease Models to Future Therapeutic Strategies
McTague, A., Rossignoli, G., Ferrini, A., Barral, S., & Kurian, M. A. (2021) · Frontiers in Genome Editing · doi:10.3389/fgeed.2021.630600 · Cited by 67
Organs to Cells and Cells to Organoids: The Evolution of in vitro Central Nervous System Modelling
Pacitti, D., Privolizzi, R., & Bax, B. E. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00129 · Cited by 66
3D Bioprinted Human Cortical Neural Constructs Derived from Induced Pluripotent Stem Cells
Salaris, F., Colosi, C., Brighi, C., Soloperto, A., de Turris, V., Benedetti, M. C., Ghirga, S., Rosito, M., Angelantonio, S. D., & Rosa, A. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8101595 · Cited by 67
Yuan, Y., Li, L., Cheng, Q., Diao, F., Zeng, Q., Yang, X., Wu, Y., Zhang, H., Huang, M., Chen, J., et al. (2020) · Cell Research · doi:10.1038/s41422-020-0283-z · Cited by 69
Bioengineered embryoids mimic post-implantation development in vitro
Girgin, M., Broguière, N., Hoehnel, S., Brandenberg, N., Mercier, B., Arias, A. M., & Lütolf, M. P. (2021) · Nature Communications · doi:10.1038/s41467-021-25237-8 · Cited by 66
Dissecting the complexities of Alzheimer disease with in vitro models of the human brain
Blanchard, J., Victor, M. B., & Tsai, L. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00578-6 · Cited by 68
Elgueta, D., Murgas, P., Riquelme, E. M., Yang, G., & Cancino, G. I. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.816619 · Cited by 70
From engineered heart tissue to cardiac organoid
Cho, J., Lee, H., Rah, W., Chang, H., & Yoon, Y. (2022) · Theranostics · doi:10.7150/thno.67661 · Cited by 70
Xu, Y., Kuppe, C., Perales-Patón, J., Hayat, S., Kranz, J., Abdallah, A. T., Nagai, J. S., Li, Z., Peisker, F., Saritas, T., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01202-z · Cited by 71
The immunobiology of herpes simplex virus encephalitis and post-viral autoimmunity
Cleaver, J., Jeffery, K. J., Klenerman, P., Lim, M. J., Handunnetthi, L., Irani, S. R., & Handel, A. E. (2023) · Brain · doi:10.1093/brain/awad419 · Cited by 74
Mutations in CDK 5 RAP 2 cause Seckel syndrome
Yigit, G., Brown, K. E., Kayserili, H., Pohl, E., Caliebe, A., Zahnleiter, D., Rosser, E. M., Bögershausen, N., Uyguner, Z. O., Altunoğlu, U., et al. (2015) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.158 · Cited by 67
Shared effects of DISC1 disruption and elevated WNT signaling in human cerebral organoids
Srikanth, P., Lagomarsino, V. N., Muratore, C., Ryu, S. C., He, A., Taylor, W. M., Zhou, C. Q., Arellano, M., & Young‐Pearse, T. L. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0122-x · Cited by 69
An update on human astrocytes and their role in development and disease
de Majo, M., Koontz, M., Rowitch, D. H., & Ullian, E. M. (2020) · Glia · doi:10.1002/glia.23771 · Cited by 69
Organotypic culture assays for murine and human primary and metastatic-site tumors
Padmanaban, V., Grasset, E. M., Neumann, N. M., Fraser, A. K., Henriet, E., Matsui, W. H., Tran, P. T., Cheung, K. J., Georgess, D., & Ewald, A. J. (2020) · Nature Protocols · doi:10.1038/s41596-020-0335-3 · Cited by 67
Utility of iPSC-Derived Cells for Disease Modeling, Drug Development, and Cell Therapy
Nicholson, M. W., Ting, C.-Y., Chan, D. Z. H., Cheng, Y.-C., Lee, Y.-C., Hsu, C.-C., Huang, C.-Y., & Hsieh, P. C. H. (2022) · Cells · doi:10.3390/cells11111853 · Cited by 65
“These 3D “organoids” are often found to have instructive morphogenetic cues resulting in self organization similarly found in vivo [53,54].”
BackgroundYakoub, A. M. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.249283 · Cited by 67
Atypical Neurogenesis in Induced Pluripotent Stem Cells From Autistic Individuals
Adhya, D., Swarup, V., Nagy, R., Polit, L. D., Shum, C., Valencia-Alarcón, E. P., Jozwik, K. M., Méndez, M. A., Horder, J., Loth, E., et al. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.06.014 · Cited by 65
Brain organoids, consciousness, ethics and moral status
Jeziorski, J. J., Brandt, R., Evans, J. H., Campana, W. M., KALICHMAN, M. W., Thompson, E. T., Goldstein, L. S. B., Koch, C., & Muotri, A. R. (2022) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2022.03.020 · Cited by 71
Spinal cord extracts of amyotrophic lateral sclerosis spread TDP-43 pathology in cerebral organoids
Tamaki, Y., Ross, J. P., Alipour, P., Castonguay, C.-E., Li, B., Catoire, H., Rochefort, D. L., Urushitani, M., Takahashi, R., Sonnen, J. A., et al. (2023) · PLoS Genetics · doi:10.1371/journal.pgen.1010606 · Cited by 67
Brain organoids and organoid intelligence from ethical, legal, and social points of view
Härtung, T., Pantoja, I. E. M., & Smirnova, L. (2024) · Frontiers in Artificial Intelligence · doi:10.3389/frai.2023.1307613 · Cited by 78
Epigenetic changes in the developing brain: Effects on behavior
Keverne, E. B., Pfaff, D. W., & Tabansky, I. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1501482112 · Cited by 68
Organoid development in cancer genome discovery
Gao, D., & Chen, Y. (2015) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2015.02.007 · Cited by 71
Nakamura, M., Shiozawa, S., Tsuboi, D., Amano, M., Watanabe, H., Maeda, S., Kimura, T., Yoshimatsu, S., Kisa, F., Karch, C. M. M., et al. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.08.011 · Cited by 64
Human Cortical Organoids Expose a Differential Function of GSK3 on Cortical Neurogenesis
Tobon, A., Villa, C. E., Cheroni, C., Trattaro, S., Caporale, N., Conforti, P., Iennaco, R., Lachgar-Ruiz, M., Rigoli, M. T., de la Cruz, B. M., et al. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.09.005 · Cited by 62
Present Application and Perspectives of Organoid Imaging Technology
Fei, K., Zhang, J., Yuan, J., & Xiao, P. (2022) · Bioengineering · doi:10.3390/bioengineering9030121 · Cited by 65
Blin, G., Wisniewski, D., Picart, C., Théry, M., Pucéat, M., & Lowell, S. (2018) · Development · doi:10.1242/dev.166025 · Cited by 66
Studying Human Neurodevelopment and Diseases Using 3D Brain Organoids
Tian, A., Muffat, J., & Li, Y. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.0519-19.2019 · Cited by 68
Organoid models of glioblastoma: advances, applications and challenges.
Zhang, C., Jin, M.-Z., Zhao, J., Chen, J., & Jin, W. (2020) · PubMed Central · Cited by 66
Behavior and lineage progression of neural progenitors in the mammalian cortex
Lin, Y., Yang, J., Shen, Z., Ma, J., Simons, B. D., & Shi, S. (2020) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2020.10.017 · Cited by 63
Human Brain Organoids-on-Chip: Advances, Challenges, and Perspectives for Preclinical Applications
Castiglione, H., Vigneron, P.-A., Baquerre, C., Yates, F., Rontard, J., & Honegger, T. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14112301 · Cited by 73
Saglam‐Metiner, P., Devamoglu, U., Filiz, Y., Akbari, S., Beceren, G., Bağca, B. G., Yaldiz, B., Yanasik, S., Avcı, Ç. B., Erdal, E., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-04547-1 · Cited by 69
Nuclease‐mediated genome editing: At the front‐line of functional genomics technology
Sakuma, T., & Woltjen, K. (2014) · Development Growth & Differentiation · doi:10.1111/dgd.12111 · Cited by 70
Pluripotent stem cell-based disease modeling: current hurdles and future promise
Zeltner, N., & Studer, L. (2015) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2015.10.008 · Cited by 68
Badenes, S. M., Fernandes, T. G., Rodrigues, C. A. V., Diogo, M. M., & Cabral, J. M. S. (2016) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2016.07.023 · Cited by 65
Organoid technologies meet genome engineering
Nie, J., & Hashino, E. (2017) · EMBO Reports · doi:10.15252/embr.201643732 · Cited by 69
Metadata
- Authors
- 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.
- Affiliations
- Institute of Molecular Biotechnology (AT)
- Institute of Genetics and Cancer (GB)
- Wellcome Sanger Institute (GB)
- St George's, University of London (GB)
- Corresponding author
- Knoblich, Juergen A.
- ORCID
- Venue
- Nature
- Published
- 2013-08-28
- Volume
- 501
- Issue
- 7467
- Pages
- 373-379
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3817409
- OpenAlex
- W2018286352
- Cited by
- 5,372
- References
- 57
- Citations by year
- 2026: 446 · 2025: 575 · 2024: 543 · 2023: 560 · 2022: 544 · 2021: 572 · 2020: 512 · 2019: 383 · 2018: 346 · 2017: 302 · 2016: 239 · 2015: 175 · 2014: 138 · 2013: 31
- FWCI
- 72.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (WT 098051)
- Lister Institute of Preventive Medicine
- Österreichischen Akademie der Wissenschaften
- Austrian Science Fund
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- brain organoids, human brain development, microcephaly, pluripotent stem cells, induced pluripotent stem cells, three-dimensional organoid culture, cortical development, neuronal differentiation, patient-derived disease model
- MeSH terms
- Animals, Brain, Cerebral Cortex, Humans, Microcephaly, Models, Biological, Neurons, Organoids, Tissue Culture Techniques, Mice, Neurogenesis, Induced Pluripotent Stem Cells, Neural Stem Cells
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