Altered patterning of trisomy 21 interneuron progenitors
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Abstract
Individuals with Down syndrome (DS; Ts21), the most common genetic cause of intellectual disability, have smaller brains that reflect fewer neurons at pre- and post-natal stages, implicating impaired neurogenesis during development. Our stereological analysis of adult DS cortex indicates a reduction of calretinin-expressing interneurons. Using Ts21 human induced pluripotent stem cells (iPSCs) and isogenic controls, we find that Ts21 progenitors generate fewer COUP-TFII+ progenitors with reduced proliferation. Single-cell RNA sequencing of Ts21 progenitors confirms the altered specification of progenitor subpopulations and identifies reduced WNT signaling. Activation of WNT signaling partially restores the COUP-TFII+ progenitor population in Ts21, suggesting that altered WNT signaling contributes to the defective development of cortical interneurons in DS.
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Reduced neurogenesis occurs in both humans with DS-AD and DS mouse models.
“We expected to find specific alterations in the DG due to reduced neurogenesis in both humans with DS‐AD and DS mouse models. 38 , 39”
From Disruption of hippocampal upstream regulators of mTOR and insulin pathways in Down syndrome with Alzheimer's disease neuropathology: Preliminary observations (2026) · cites this paper as [38]
The Introduction (page unavailable) links fewer neurons in people with Down syndrome to reduced neurogenesis. The References section (page unavailable) lists a study of decreased cell proliferation in the dentate gyrus of Down syndrome fetuses and in Ts65Dn mice. Neither passage establishes reduced neurogenesis specifically in humans with DS-AD, so the claim extends beyond what this paper supports. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSeveral studies have shown that fewer interneurons are present in the cortex of individuals with Down syndrome than in controls, suggesting that reduced generation of interneurons contributes to the overall reduced neurogenesis in Down syndrome.
“Several studies have shown that fewer interneurons are present in the cortex of individuals with DS44,46,84 than in that of controls, suggesting that reduced generation of interneurons contributes to the overall reduced neurogenesis in DS.”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [84]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredEvidence for specific deficits in late-born upper-layer neurons in Down syndrome from observations of post-mortem tissue suggests that specific temporally defined progenitors are affected.
“Evidence for specific deficits in late-born upper-layer neurons in DS from observations of post-mortem tissue further suggests that specific temporally defined progenitors are affected41,84.”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [84]
Evidence from induced pluripotent stem cells differentiated to ventral forebrain-like interneuron progenitors indicates that the number of progenitors produced is different in the presence of trisomy 21.
“Evidence from iPSCs differentiated to ventral forebrain-like interneuron progenitors indicates that the number of progenitors that are produced is different in the presence of T21 (84,90,91).”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [84]
The S6 kinases (S6Ks) are activated by the mTORC1 complex acting as effectors.
“The S6 kinases (S6Ks) are activated by the mTORC1 complex acting as effectors.”
From Disruption of hippocampal upstream regulators of mTOR and insulin pathways in Down syndrome with Alzheimer's disease neuropathology: Preliminary observations (2026) · cites this paper as [38]
The Results sections on Ts21 progenitors discuss WNT and SHH signaling, but do not address whether mTORC1 activates S6 kinases. Searches for mTORC1, S6 kinase activation, and S6Ks returned no passage supporting the claim; page numbers were unavailable in our copy. (LLM, conf=0.72)
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Metascape provides a biologist-oriented resource for the analysis of systems-level datasets
Zhou, Y., Zhou, B., Pache, L., Chang, M., Khodabakhshi, A. H., Tanaseichuk, O., Benner, C., & Chanda, S. K. (2019) · Nature Communications · doi:10.1038/s41467-019-09234-6 · Cited by 14,611 · see citing works
Integrating single-cell transcriptomic data across different conditions, technologies, and species
Butler, A., Hoffman, P., Smibert, P., Papalexi, E., & Satija, R. (2018) · Nature Biotechnology · doi:10.1038/nbt.4096 · Cited by 13,174 · see citing works
Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,949 · see citing works
West, M. J., Slomianka, L., & Gundersen, H. J. G. (1991) · The Anatomical Record · doi:10.1002/ar.1092310411 · Cited by 2,994 · see citing works
Interneuron dysfunction in psychiatric disorders
Marín, O. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3155 · Cited by 1,190 · see citing works
Cortical interneurons that specialize in disinhibitory control
Pi, H.-J., Hangya, B., Kvitsiani, D., Sanders, J. I., Huang, Z. J., & Kepecs, A. (2013) · Nature · doi:10.1038/nature12676 · Cited by 1,136 · see citing works
Integrative functional genomic analysis of human brain development and neuropsychiatric risks
Li, M., Santpere, G., Imamura Kawasawa, Y., Evgrafov, O. V., Gulden, F. O., Pochareddy, S., Sunkin, S. M., Li, Z., Shin, Y., Zhu, Y., et al. (2018) · Science · doi:10.1126/science.aat7615 · Cited by 810 · see citing works
Self-citationOrigins of Cortical Interneuron Subtypes
Xu, Q., Cobos, I., De La Cruz, E., Rubenstein, J. L., & Anderson, S. A. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.5667-03.2004 · Cited by 639 · see citing works
Maroof, A. M., Keros, S., Tyson, J. A., Ying, S.-W., Ganat, Y. M., Merkle, F. T., Liu, B., Goulburn, A., Stanley, E. G., Elefanty, A. G., et al. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.04.008 · Cited by 596 · see citing works
Fate mapping Nkx2.1‐lineage cells in the mouse telencephalon
Xu, Q., Tam, M., & Anderson, S. A. (2007) · The Journal of Comparative Neurology · doi:10.1002/cne.21529 · Cited by 560 · see citing works
Nicholas, C. R., Chen, J., Tang, Y., Southwell, D. G., Chalmers, N., Vogt, D. L., Arnold, C. M., Chen, Y.-J. J., Stanley, E. G., Elefanty, A. G., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.04.005 · Cited by 513 · see citing works
Developmental diversification of cortical inhibitory interneurons
Mayer, C., Hafemeister, C., Bandler, R. C., Machold, R., Batista Brito, R., Jaglin, X., Allaway, K., Butler, A., Fishell, G., & Satija, R. (2018) · Nature · doi:10.1038/nature25999 · Cited by 492 · see citing works
Cognitive deficits and associated neurological complications in individuals with Down's syndrome
Lott, I. T., & Dierssen, M. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70112-5 · Cited by 484 · see citing works
Extensive migration of young neurons into the infant human frontal lobe
Paredes, M. F., James, D., Gil-Perotin, S., Kim, H., Cotter, J. A., Ng, C., Sandoval, K., Rowitch, D. H., Xu, D., McQuillen, P. S., et al. (2016) · Science · doi:10.1126/science.aaf7073 · Cited by 391 · see citing works
Non-epithelial stem cells and cortical interneuron production in the human ganglionic eminences
Hansen, D. V., Lui, J. H., Flandin, P., Yoshikawa, K., Rubenstein, J. L., Alvarez-Buylla, A., & Kriegstein, A. R. (2013) · Nature Neuroscience · doi:10.1038/nn.3541 · Cited by 328 · see citing works
Subcortical origins of human and monkey neocortical interneurons
Ma, T., Wang, C., Wang, L., Zhou, X., Tian, M., Zhang, Q., Zhang, Y., Li, J., Liu, Z., Cai, Y., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3536 · Cited by 322 · see citing works
Induction and Dorsoventral Patterning of the Telencephalon
Wilson, S. W., & Rubenstein, J. L. R. (2000) · Neuron · doi:10.1016/s0896-6273(00)00171-9 · Cited by 314 · see citing works
Li, X.-J., Zhang, X., Johnson, M. A., Wang, Z.-B., LaVaute, T. M., & Zhang, S. (2009) · Development · doi:10.1242/dev.036624 · Cited by 312 · see citing works
Self-citationTakashima, S., Becker, L. E., Armstrong, D. L., & Chan, F. (1981) · Brain Research · doi:10.1016/0006-8993(81)90314-0 · Cited by 307 · see citing works
Directed differentiation of forebrain GABA interneurons from human pluripotent stem cells
Liu, Y., Liu, H., Sauvey, C., Yao, L., Żarnowska, E. D., & Zhang, S. (2013) · Nature Protocols · doi:10.1038/nprot.2013.106 · Cited by 300 · see citing works
Self-citationWisniewski, K. E. (2005) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320370755 · Cited by 297 · see citing works
Contestabile, A., Fila, T., Ceccarelli, C., Bonasoni, P., Bonapace, L., Santini, D., Bartesaghi, R., & Ciani, E. (2007) · Hippocampus · doi:10.1002/hipo.20308 · Cited by 281 · see citing works
Deidda, G., Parrini, M., Naskar, S., Bozarth, I. F., Contestabile, A., & Cancedda, L. (2015) · Nature Medicine · doi:10.1038/nm.3827 · Cited by 268 · see citing works
Olmos-Serrano, J. L., Kang, H. J., Tyler, W. A., Silbereis, J. C., Cheng, F., Zhu, Y., Pletikos, M., Jankovic-Rapan, L., Cramer, N. P., Galdzicki, Z., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.042 · Cited by 239 · cited 4× · see citing works
“GLI3 is mis-expressed temporally during fetal cortical development; GLI3 expression is initially higher than controls and then lower than controls (Olmos-Serrano et al., 2016), consistent with altered emergence of this cluster of cells.”
BackgroundInfluentialNKX2.1 specifies cortical interneuron fate by activatingLhx6
Du, T., Xu, Q., Ocbina, P. J. R., & Anderson, S. A. (2008) · Development · doi:10.1242/dev.015123 · Cited by 220 · see citing works
Xu, Q., Guo, L., Moore, H., Waclaw, R. R., Campbell, K., & Anderson, S. A. (2010) · Neuron · doi:10.1016/j.neuron.2010.01.004 · Cited by 218 · see citing works
Development of the superior temporal neocortex is anomalous in trisomy 21
Golden, J. A., & Hyman, B. T. (1994) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199409000-00011 · Cited by 210 · see citing works
(1991) · PubMed · Cited by 209 · see citing works
(1990) · PubMed · Cited by 201 · see citing works
Boyce, R. W., Dorph‐Petersen, K., Lyck, L., & Gundersen, H. J. G. (2010) · Toxicologic Pathology · doi:10.1177/0192623310385140 · Cited by 198 · see citing works
Xu, R., Brawner, A. T., Li, S., Liu, J.-J., Kim, H., Xue, H., Pang, Z. P., Kim, W.-Y., Hart, R. P., Liu, Y., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.04.014 · Cited by 193 · see citing works
Down's syndrome: Is there a decreased population of neurons?
Ross, M. H., Galaburda, A. M., & Kemper, T. L. (1984) · Neurology · doi:10.1212/wnl.34.7.909 · Cited by 191 · see citing works
Mouse and human share conserved transcriptional programs for interneuron development
Shi, Y., Wang, M., Mi, D., Lu, T., Wang, B., Dong, H., Zhong, S., Chen, Y., Sun, L., Zhou, X., et al. (2021) · Science · doi:10.1126/science.abj6641 · Cited by 188 · see citing works
Xu, Q., Wonders, C. P., & Anderson, S. A. (2005) · Development · doi:10.1242/dev.02090 · Cited by 184 · see citing works
Genetics and Function of Neocortical GABAergic Interneurons in Neurodevelopmental Disorders
Rossignol, E. (2011) · Neural Plasticity · doi:10.1155/2011/649325 · Cited by 183 · see citing works
Distinct Origins of Neocortical Projection Neurons and Interneurons In Vivo
Anderson, S. A. (2002) · Cerebral Cortex · doi:10.1093/cercor/12.7.702 · Cited by 179 · see citing works
Dorsal-ventral patterning in the mammalian telencephalon
Campbell, K. (2003) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(03)00009-6 · Cited by 173 · see citing works
Guidi, S., Ciani, E., Bonasoni, P., Santini, D., & Bartesaghi, R. (2011) · Brain Pathology · doi:10.1111/j.1750-3639.2010.00459.x · Cited by 165 · see citing works
Kanatani, S., Yozu, M., Tabata, H., & Nakajima, K. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.2132-08.2008 · Cited by 163 · see citing works
Kesslak, J. P., Nagata, S. F., Lott, I., & Nalcioglu, O. (1994) · Neurology · doi:10.1212/wnl.44.6.1039 · Cited by 145 · see citing works
The R-spondin family of proteins: Emerging regulators of WNT signaling
Jin, Y.-R., & Yoon, J. K. (2012) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2012.09.006 · Cited by 135 · see citing works
Huo, H.-Q., Qu, Z.-Y., Yuan, F., Ma, L., Yao, L., Xu, M., Hu, Y., Ji, J., Bhattacharyya, A., Zhang, S.-C., et al. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.02.001 · Cited by 122 · see citing works
Self-citationWeitzdoerfer, R., Dierssen, M., Fountoulakis, M., & Lübec, G. (2001) · Springer eBooks · doi:10.1007/978-3-7091-6262-0_5 · Cited by 122 · see citing works
Genetic programs controlling cortical interneuron fate
Kessaris, N., Magno, L., Rubin, A. N., & Oliveira, M. G. (2014) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.12.012 · Cited by 122 · see citing works
Neurogenesis impairment: An early developmental defect in Down syndrome
Stagni, F., Giacomini, A., Emili, M., Guidi, S., & Bartesaghi, R. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.07.026 · Cited by 120 · see citing works
(1948) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.1948.tb97137.x · Cited by 117 · see citing works
Molecular basis of pharmacotherapies for cognition in Down syndrome
Gardiner, K. (2009) · TIPS - Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.10.010 · Cited by 113 · see citing works
Lodato, S., Tomassy, G. S., De Leonibus, E., Uzcategui, Y. G., Andolfi, G., Armentano, M., Touzot, A., Gaztelu, J. M., Arlotta, P., Menendez de la Prida, L., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.6580-10.2011 · Cited by 112 · see citing works
Developmental Mechanisms Underlying the Generation of Cortical Interneuron Diversity
Flames, N., & Marín, Ó. (2005) · Neuron · doi:10.1016/j.neuron.2005.04.020 · Cited by 107 · see citing works
Kim, T., Yao, R., Monnell, T. E., Cho, J.-H., Vasudevan, A., Koh, A., Peeyush, K. T., Moon, M., Datta, D., Bolshakov, V. Y., et al. (2014) · Stem Cells · doi:10.1002/stem.1704 · Cited by 106 · see citing works
The Origins of Cortical Interneurons: Mouse versus Monkey and Human
Jones, E. G. (2009) · Cerebral Cortex · doi:10.1093/cercor/bhp088 · Cited by 105 · see citing works
Hyperkalemia during Anesthesia
Wisniewski, K. E., Laure‐Kamionowska, M., & Wisniewski, H. M. (1984) · New England Journal of Medicine · doi:10.1056/nejm198411013111818 · Cited by 105 · see citing works
Cognitive functioning in relation to brain amyloid-β in healthy adults with Down syndrome
Hartley, S. L., Handen, B. L., Devenny, D. A., Hardison, R. M., Mihaila, I., Price, J. C., Cohen, A. D., Klunk, W. E., Seltzer, M. M., Johnson, S. C., et al. (2014) · Brain · doi:10.1093/brain/awu173 · Cited by 100 · see citing works
Extended Production of Cortical Interneurons into the Third Trimester of Human Gestation
Arshad, A., Vose, L. R., Vinukonda, G., Hu, F., Yoshikawa, K., Csiszár, A., Brumberg, J. C., & Ballabh, P. (2015) · Cerebral Cortex · doi:10.1093/cercor/bhv074 · Cited by 89 · see citing works
Reduced cell number in the neocortical part of the human fetal brain in Down syndrome
Larsen, K. B., Laursen, H., Græm, N., Samuelsen, G. B., Bogdanovic, N., & Pakkenberg, B. (2008) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/j.aanat.2008.05.007 · Cited by 87 · cited 1× · see citing works
“In fact, reduced neuron density has been reported in fetal DS brain (Golden and Hyman, 1994; Guidi et al., 2018; Larsen et al., 2008; Schmidt-Sidor et al., 1990; Stagni et al., 2018).”
BackgroundEvidence of Arrest of Neurogenesis and Synaptogenesis in Brains of Patients with Down's Syndrome
(1984) · New England Journal of Medicine · doi:10.1056/nejm198411013111819 · Cited by 82 · see citing works
Bhattacharyya, A., McMillan, E., Chen, S. I., Wallace, K., & Svendsen, C. N. (2009) · Developmental Neuroscience · doi:10.1159/000236899 · Cited by 79 · see citing works
Self-citationDiversity of Cortical Interneurons in Primates: The Role of the Dorsal Proliferative Niche
Radonjić, N. V., Ayoub, A. E., Memi, F., Yu, X., Maroof, A., Jakovcevski, I., Anderson, S. A., Rakic, P., & Zecevic, N. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.11.026 · Cited by 74 · see citing works
Spatio-temporal extension in site of origin for cortical calretinin neurons in primates
Hladnik, A., Džaja, D., Darmopil, S., Jovanov-MiloÅ¡ević, N., & Petanjek, Z. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00050 · Cited by 72 · see citing works
Neocortical calretinin neurons in primates: increase in proportion and microcircuitry structure
aja, D. D. ⁄., Hladnik, A., Bičanić, I., Baković, M., & Petanjek, Z. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00103 · Cited by 69 · see citing works
Davidoff, L. M. (1928) · Archives of Neurology And Psychiatry · doi:10.1001/archneurpsyc.1928.02210180080004 · Cited by 65 · see citing works
GABAergic over-inhibition, a promising hypothesis for cognitive deficits in Down syndrome
Martín, J. Z. D. S., Delabar, J. M., Bacci, A., & Potier, M. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.10.002 · Cited by 64 · see citing works
Guet-McCreight, A., Skinner, F. K., & Topolnik, L. (2020) · Frontiers in Neural Circuits · doi:10.3389/fncir.2020.00032 · Cited by 64 · see citing works
Practical approaches to stereology in the setting of aging- and disease-related brain banks
Perl, D. P., Good, P. F., Bussière, T., Morrison, J. H., ERWIN, J. M., & Hof, P. R. (2000) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(00)00077-6 · Cited by 61 · see citing works
Treating enhanced GABAergic inhibition in Down syndrome: Use of GABA α5-selective inverse agonists
Martínez-Cué, C., Delatour, B., & Potier, M.-C. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.12.008 · Cited by 58 · see citing works
The Contribution of the Ganglionic Eminence to the Neuronal Cell Types of the Cerebral Cortex
Parnavelas, J. G., Anderson, S. A., Lavdas, A. Α., Grigoriou, M. E., Pachnis, V., & Rubenstein, J. L. R. (2000) · Novartis Foundation symposium · doi:10.1002/0470846631.ch10 · Cited by 57 · see citing works
Shh Maintains Nkx2.1 in the MGE by a Gli3-Independent Mechanism
Gulácsi, A., & Anderson, S. A. (2006) · Cerebral Cortex · doi:10.1093/cercor/bhk018 · Cited by 57 · see citing works
The Structure of the Cerebral Cortex in Down's Syndrome – A quantitative analysis –
Colon, E. J. (1972) · Neuropediatrics · doi:10.1055/s-0028-1091775 · Cited by 56 · see citing works
Tcf7L2 is essential for neurogenesis in the developing mouse neocortex
Chodelkova, O., Mašek, J., Kořínek, V., Kozmík, Z., & Machoň, O. (2018) · Neural Development · doi:10.1186/s13064-018-0107-8 · Cited by 53 · see citing works
Becker, L. E. (1991) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100031644 · Cited by 52 · see citing works
Abnormal development of the inferior temporal region in fetuses with Down syndrome
Guidi, S., Giacomini, A., Stagni, F., Emili, M., Uguagliati, B., Bonasoni, M. P., & Bartesaghi, R. (2018) · Brain Pathology · doi:10.1111/bpa.12605 · Cited by 47 · see citing works
COUP-TFII Expressing Interneurons in Human Fetal Forebrain
Reinchisi, G., Ijichi, K., Glidden, N. C., Jakovčevski, I., & Zečević, N. (2011) · Cerebral Cortex · doi:10.1093/cercor/bhr359 · Cited by 43 · see citing works
Cairney, C. J., Sanguinetti, G., Ranghini, E. J., Chantry, A., Nostro, M. C., Bhattacharyya, A., Svendsen, C. N., Keith, W. N., & Bellantuono, I. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.01.015 · Cited by 42 · see citing works
Self-citationThe nuclear receptors COUP-TF: a long-lasting experience in forebrain assembly
Alfano, C., Magrinelli, E., Harb, K., & Studer, M. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1320-6 · Cited by 38 · see citing works
Reducing Gabaergic Inhibition Restores Cognitive Functions in a Mouse Model of Down Syndrome
Potier, M.-C., Braudeau, J., Dauphinot, L., & Delatour, B. (2014) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/18715273113126660185 · Cited by 34 · see citing works
Rong, X., Chen, C., Zhou, P., Zhou, Y., Li, Y., Lu, L., Liu, Y., Zhou, J., & Duan, C. (2014) · PLoS ONE · doi:10.1371/journal.pone.0099514 · Cited by 27 · see citing works
Downregulated Wnt/β-catenin signalling in the Down syndrome hippocampus
Grannò, S., Nixon‐Abell, J., Berwick, D. C., Tosh, J., Heaton, G., Almudimeegh, S., Nagda, Z., Rain, J., Zanda, M., Plagnol, V., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-43820-4 · Cited by 25 · see citing works
Magnetic resonance imaging of the aging brain in Down syndrome.
Emerson, J. F., Kesslak, J. P., Chen, P. C., & Lott, I. T. (1995) · PubMed · Cited by 21 · see citing works
Neuropathology in Patients with Congenital Heart Disease and Down Syndrome
Mito, T., Pereyra, P. M., & Becker, L. E. (1991) · Pediatric Pathology · doi:10.3109/15513819109065483 · Cited by 19 · see citing works
West, M. J. (2013) · Cold Spring Harbor Protocols · doi:10.1101/pdb.top071852 · Cited by 13 · see citing works
Usp16 modulates Wnt signaling in primary tissues through Cdkn2a regulation
Adorno, M., di Robilant, B. N., Sikandar, S. S., Acosta, V. H., Antony, J., Heller, C. H., & Clarke, M. F. (2018) · Scientific Reports · doi:10.1038/s41598-018-34562-w · Cited by 12 · see citing works
Determination of Cell Fate within the Telencephalon
Anderson, S. A. (2002) · Chemical Senses · doi:10.1093/chemse/27.6.573 · Cited by 8 · see citing works
Flagged first, then by citations
2 of the 84 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Neurodevelopment in Down syndrome: Concordance in humans and models
Klein, J. A., & Haydar, T. F. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.941855 · Cited by 47 · see citing works
Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2
Shaker, M. R., Slonchak, A., Al-mhanawi, B., Morrison, S. D., Sng, J. D. J., Cooper-White, J. J., Khromykh, A. A., & Wolvetang, E. J. (2024) · Science Advances · doi:10.1126/sciadv.adj4735 · Cited by 32 · see citing works
Consequences of trisomy 21 for brain development in Down syndrome
Russo, M. L., Sousa, A. M. M., & Bhattacharyya, A. (2024) · Nature Reviews Neuroscience · doi:10.1038/s41583-024-00866-2 · Cited by 28 · see citing works
Self-citationRastogi, M., Bartolucci, M., Nanni, M., Aloisio, M., Vozzi, D., Petretto, A., Contestabile, A., & Cancedda, L. (2024) · Neuron · doi:10.1016/j.neuron.2024.05.002 · Cited by 26 · see citing works
Galiakberova, A. A., Brovkina, O. I., Kondratyev, N. V., Artyuhov, A., Momotyuk, E., Kulmukhametova, O. N., Lagunin, A. A., Shilov, B. V., Zadorozhny, A. D., Zakharov, I. S., et al. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1037902 · Cited by 20 · see citing works
Guerreiro, S. R., & Maciel, P. (2023) · Cells · doi:10.3390/cells12040538 · Cited by 20 · see citing works
Transcriptional consequences of trisomy 21 on neural induction
Martinez, J. L., Piciw, J. G., Crockett, M., Sorci, I. A., Makwana, N., Sirois, C. L., Giffin-Rao, Y., & Bhattacharyya, A. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1341141 · Cited by 15 · see citing works
Self-citationWatson, L. A., & Meharena, H. S. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.1198129 · Cited by 13 · see citing works
A dynamic in vitro model of Down syndrome neurogenesis with trisomy 21 gene dosage correction
Bansal, P., Banda, E. C., Glatt-Deeley, H. R., Stoddard, C. E., Linsley, J. W., Arora, N., Deleschaux, C., Ahern, D. T., Kondaveeti, Y., Massey, R. E., et al. (2024) · Science Advances · doi:10.1126/sciadv.adj0385 · Cited by 13 · see citing works
Shaking up the silence: consequences of HMGN1 antagonizing PRC2 in the Down syndrome brain
Farley, S. J., Grishok, A., & Zeldich, E. (2022) · Epigenetics & Chromatin · doi:10.1186/s13072-022-00471-6 · Cited by 13 · see citing works
Shao, L., Gao, F., Chinnasamy, V., Kazuki, Y., Oshimura, M., Reeves, R. H., & Stafstrom, C. E. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106198 · Cited by 12 · see citing works
Campbell, N. B., Patel, Y., Moore, T. L., Medalla, M., & Zeldich, E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043477 · Cited by 8 · see citing works
Rusu, B., Kukreja, B., Wu, T., Dan, S. J., Feng, M.-Y., & Kalish, B. (2023) · eNeuro · doi:10.1523/eneuro.0147-23.2023 · Cited by 2 · see citing works
Huang, T., Fakurazi, S., Cheah, P.-S., & Ling, K. (2025) · Scientific Reports · doi:10.1038/s41598-025-87314-y · Cited by 9 · see citing works
Lee, S. E., Baxter, L. L., Duran, M. I., Morris, S. D., Mosley, I. A., Fuentes, K. A., Pennings, J., Guedj, F., & Bianchi, D. W. (2024) · Human Molecular Genetics · doi:10.1093/hmg/ddae160 · Cited by 3 · see citing works
The Hallmarks of Aneuploidy in Cancer and Congenital Syndromes
Cheng, P., Singh, K., Reeves, R. H., & Davoli, T. (2025) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-111723-103557 · Cited by 5 · see citing works
Single-cell atlas of the developing Down syndrome brain cortex
Lattke, M., Tan, W. L., Sukumaran, S. K., Utami, K. H., Sintes, M., Sakthivel, S., Tan, J., Lim, A. T. J., Bansal, V. A., Rekopoulou, K., et al. (2026) · Nature Medicine · doi:10.1038/s41591-026-04211-1 · Cited by 8 · see citing works
Raza, M. A., Folz, A., Victorino, D. B., Xing, Z., Chen, X., Zuo, X., Borden, L. K., Potier, M., Mobley, W. C., Dierssen, M., et al. (2026) · STAR Protocols · doi:10.1016/j.xpro.2026.104717 · Cited by 5 · see citing works
Muza, P. M., Bush, D., Pérez-González, M., Zouhair, I., Cleverley, K., Sopeña, M. L., Aoidi, R., West, S. J., Good, M. A., Tybulewicz, V. L. J., et al. (2023) · iScience · doi:10.1016/j.isci.2023.106073 · Cited by 5 · see citing works
Vertebrate and Invertebrate Animal Models for the Study of Down Syndrome
Granholm, A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26168092 · Cited by 3 · see citing works
West, N. R., Lindberg, M. F., Dairou, J., MacGregor, S., Puthireddy, S., Meijer, L., & Bhattacharyya, A. (2026) · Disease Models & Mechanisms · doi:10.1242/dmm.052740 · Cited by 3 · see citing works
Self-citationLithium restores nuclear REST and Mitigates oxidative stress in down syndrome iPSC-Derived neurons
Lam, X.-J., Maniam, S., Ling, K., & Cheah, P.-S. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2024.12.061 · Cited by 3 · see citing works
Trisomy 21 Impairs Synchronized Activity in Human Down Syndrome Cortical Excitatory Neuron NetworksPreprint
Peter, M., Real, R., Strano, A., Robinson, H. P. C., Smith, M. A., Barnes, S. J., Dutta, T., Paola, V. D., & Livesey, F. J. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.27.630530 · Cited by 2 · see citing works
Development of Molecular Neuropathology in Down Syndrome across the Lifespan
Bhattacharyya, A., de la Torre-Ubieta, L., Zhu, Y., Head, E., Swarup, V., & Sousa, A. M. M. (2025) · Journal of Neuroscience · doi:10.1523/jneurosci.1365-25.2025 · Cited by 3 · see citing works
Self-citationThe restoration of REST inhibits reactivity of Down syndrome iPSC-derived astrocytes
Huang, T., Fakurazi, S., Cheah, P.-S., & Ling, K. (2025) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2025.1552819 · Cited by 2 · see citing works
Perry, J. C., & Vann, S. D. (2024) · Neuroscience · doi:10.1016/j.neuroscience.2024.08.004 · Cited by 2 · see citing works
REST deficiency and neurogenic-to-gliogenic shift in down syndrome human cerebral organoids
Huang, T., Lim, C.-T., Li, W., Fakurazi, S., Mason, J. O., Cheah, P.-S., Li, Y., & Ling, K. (2026) · Molecular Brain · doi:10.1186/s13041-026-01313-2 · Cited by 1 · see citing works
Plećaš, A., Gough, G., Grčević, D., Jackowiak, H., Skieresz‐Szewczyk, K., Horaček, M., Šimunić, I., Krsnik, Ž., Mitrečić, D., Murray, A., et al. (2026) · Cell Death and Disease · doi:10.1038/s41419-026-08956-y · Cited by 1 · see citing works
Wang, X., Lalli, M. A., Thopte, U., & Buxbaum, J. D. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.25.614184 · Cited by 1 · see citing works
Nordbeck, A. J., Martá‐Ariza, M., Ek Olofsson, H., Kanshin, E., Ueberheide, B., Jones, K., Sanford, B., Hamlett, E. D., Head, E., Mufson, E. J., et al. (2026) · Alzheimer's & Dementia · doi:10.1002/alz.71776
“38,39 The current analysis focused only on mTOR/INS pathways within the DG neuronal cluster (pink cluster in Figure 1C,D).”
Perry, J. C., & Vann, S. D. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.02.01.578360
Realizing the potential of exploiting human IPSCs and their derivatives in research of Down syndrome
Wang, Y., Ni, J., LIU, Y., Liao, D.-Y., Zhou, Q., Ji, X., NIU, G., & Ni, Y. (2023) · Biocell · doi:10.32604/biocell.2023.043781
Jandy, M., Hu, H., Liu, Y., & Bhattacharyya, A. (2025) · Springer eBooks · doi:10.1007/978-3-031-78611-2_7
Self-citationLattke, M., Tan, W. L., Sukumaran, S. K., Utami, K. H., Sintes, M., Sakthivel, S., Tan, J., Lim, A. T. J., Bansal, V. A., Rekopoulou, K., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.29.696602
Leucettinib-21 decreases dosage effects of DYRK1A in human trisomy 21 iPSC-derived neural cellsPreprint
West, N. R., Lindberg, M. F., Dairou, J., MacGregor, S., Puthireddy, S., Meijer, L., & Bhattacharyya, A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.05.704014
Self-citationAberrant chromatin remodeling influences human neural cell fate change in Trisomy 21Preprint
Klein, J. A., Upadhya, S., Nathanson, A. J., Silvian, D., Zaniewski, E. F., Morris, R., Haas, W., & Barrett, L. E. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.01.729170
Plećaš, A., Gough, G., Kunštek, S., Babić, M., Murray, A., Nižetić, D., & Alić, I. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1963992
- Authors
- Giffin-Rao, Y., Sheng, J., Strand, B., Xu, K., Huang, L., Medo, M., Risgaard, K. A., Dantinne, S., Mohan, S., Keshan, A., Daley, R. A., Levesque, B., Amundson, L., Reese, R., Sousa, A. M. M., Tao, Y., Wang, D., Zhang, S.-C., & Bhattacharyya, A.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Bhattacharyya, Anita
- ORCID
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2022-06
- Volume
- 17
- Issue
- 6
- Pages
- 1366-1379
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC9214050
- OpenAlex
- W4281558139
- Cited by
- 38
- References
- 84
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 11 · 2023: 8 · 2022: 2
- FWCI
- 2.66
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- University of Wisconsin Madison
- College of Engineering, University of Wisconsin-Madison
- National Institutes of Health (1R01HD106197, R03HD083538, R21NS105339)
- Wisconsin Alumni Research Foundation
- National Institute of Child Health and Human Development (U54 HD090256)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- Down syndrome, COUP-TFII, Wnt signaling, calretinin, neurogenesis, intellectual disability, iPSC-derived neurons, progenitor cell proliferation
- MeSH terms
- Adult, Down Syndrome, Humans, Interneurons, Neurons, Trisomy, Neurogenesis, Induced Pluripotent Stem Cells
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