Biphasic cell cycle defect causes impaired neurogenesis in down syndrome
Open accessAbstract
Impaired neurogenesis in Down syndrome (DS) is characterized by reduced neurons, increased glial cells, and delayed cortical lamination. However, the underlying cause for impaired neurogenesis in DS is not clear. Using both human and mouse iPSCs, we demonstrate that DS impaired neurogenesis is due to biphasic cell cycle dysregulation during the generation of neural progenitors from iPSCs named the “neurogenic stage” of neurogenesis. Upon neural induction, DS cells showed reduced proliferation during the early phase followed by increased proliferation in the late phase of the neurogenic stage compared to control cells. While reduced proliferation in the early phase causes reduced neural progenitor pool, increased proliferation in the late phase leads to delayed post mitotic neuron generation in DS. RNAseq analysis of late-phase DS progenitor cells revealed upregulation of S phase-promoting regulators, Notch, Wnt, Interferon pathways, and REST, and downregulation of several genes of the BAF chromatin remodeling complex. NFIB and POU3F4, neurogenic genes activated by the interaction of PAX6 and the BAF complex, were downregulated in DS cells. ChIPseq analysis of late-phase neural progenitors revealed aberrant PAX6 binding with reduced promoter occupancy in DS cells. Together, these data indicate that impaired neurogenesis in DS is due to biphasic cell cycle dysregulation during the neurogenic stage of neurogenesis.
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Cell cycle dynamics are altered in Down syndrome and are altered differentially at different developmental stages.
“This suggested that cell cycle dynamics are altered in DS and that they are altered differentially at different developmental stages.”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [65]
BrdU pulse labelling of trisomy 21 induced pluripotent stem cell-derived progenitors revealed that the proportion of neural progenitor cells in S phase of the cell cycle can vary across different stages of their development in vitro.
“Additional evidence, which shows that decreased proliferation of progenitors can lead to the generation of fewer neurons in DS, comes from BrdU pulse labelling of T21 iPSC-derived progenitors, which revealed that the proportion of NPCs in S phase of the cell cycle, the period of protein synthesis before mitosis or cell division, can vary across different stages of their development in vitro65.”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [65]
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Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · see citing works
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · see citing works
clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters
Yu, G., Wang, L.-G., Han, Y., & He, Q.-Y. (2012) · OMICS: A Journal of Integrative Biology · doi:10.1089/omi.2011.0118 · Cited by 36,259 · see citing works
featureCounts: an efficient general purpose program for assigning sequence reads to genomic features
Liao, Y., Smyth, G. K., & Shi, W. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btt656 · Cited by 27,219 · see citing works
Takahashi, K., & Yamanaka, S. (2006) · Cell · doi:10.1016/j.cell.2006.07.024 · Cited by 26,673 · see citing works
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849 · see citing works
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007) · Cell · doi:10.1016/j.cell.2007.11.019 · Cited by 20,221 · see citing works
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386 · see citing works
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197 · see citing works
ChIPseeker: an R/Bioconductor package for ChIP peak annotation, comparison and visualization
Yu, G., Wang, L.-G., & He, Q. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv145 · Cited by 4,399 · see citing works
The Glial Nature of Embryonic and Adult Neural Stem Cells
Kriegstein, A., & Alvarez-Buylla, A. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135600 · Cited by 2,475 · see citing works
The cell biology of neurogenesis
Götz, M., & Huttner, W. B. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1739 · Cited by 2,130 · see citing works
Control of cell cycle transcription during G1 and S phases
Bertoli, C., Skotheim, J. M., & de Bruin, R. A. M. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3629 · Cited by 1,510 · see citing works
Transient expression of doublecortin during adult neurogenesis
Brown, J. P., Couillard‐Després, S., Cooper‐Kuhn, C. M., Winkler, J., Aigner, L., & Kuhn, H. G. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10874 · Cited by 1,494 · see citing works
HES and HERP families: Multiple effectors of the notch signaling pathway
Iso, T., Kedes, L., & Hamamori, Y. (2003) · Journal of Cellular Physiology · doi:10.1002/jcp.10208 · Cited by 1,240 · see citing works
ChIPpeakAnno: a Bioconductor package to annotate ChIP-seq and ChIP-chip data
Zhu, L., Gazin, C., Lawson, N., Pagès, H., Lin, S. M., Lapointe, D. S., & Green, M. R. (2010) · BMC Bioinformatics · doi:10.1186/1471-2105-11-237 · Cited by 1,144 · see citing works
Gleeson, J. G., Allen, K. M., Fox, J. W., Lamperti, E. D., Berkovic, S. F., Scheffer, I. E., Cooper, E. C., Dobyns, W. B., Minnerath, S., Ross, M. E., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)80899-5 · Cited by 1,091 · see citing works
Regulation of gliogenesis in the central nervous system by the JAK-STAT signaling pathway.
Bonni, A., Sun, Y., Nadal-Vicens, M., Bhatt, A. S., Frank, D., Rozovsky, I., Stahl, N., Yancopouloš, G., & Greenberg, M. (1997) · Science · doi:10.1126/science.278.5337.477 · Cited by 1,050 · see citing works
Francis, F., Koulakoff, A., Boucher, D., Chafey, P., Schaar, B. T., Vinet, M. C., Friocourt, G., McDonnell, N., Reiner, O., Kahn, A., et al. (1999) · Neuron · doi:10.1016/s0896-6273(00)80777-1 · Cited by 1,000 · see citing works
A mouse model for Down syndrome exhibits learning and behaviour deficits
Reeves, R. H., Irving, N. G., Moran, T. H., Wohn, A., Kitt, C., Sisodia, S. S., Schmidt, C., Bronson, R. T., & Davisson, M. T. (1995) · Nature Genetics · doi:10.1038/ng1095-177 · Cited by 913 · see citing works
MLL-rearranged Leukemia is Dependent on Aberrant H3K79 Methylation by DOT1L
Bernt, K., Zhu, N., Sinha, A., Vempati, S., Faber, J., Krivtsov, A., Feng, Z.-H., Punt, N., Daigle, A., Bullinger, L., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.06.010 · Cited by 896 · see citing works
Qian, X., Shen, Q., Goderie, S. K., He, W., Capela, A., Davis, A. A., & Temple, S. (2000) · Neuron · doi:10.1016/s0896-6273(00)00086-6 · Cited by 866 · see citing works
Wnt signaling and stem cell control
Nusse, R. (2008) · Cell Research · doi:10.1038/cr.2008.47 · Cited by 847 · see citing works
Lessard, J., Wu, J. I., Ranish, J. A., Wan, M., Winslow, M. M., Staahl, B. T., Wu, H., Aebersold, R., Graef, I. A., & Crabtree, G. R. (2007) · Neuron · doi:10.1016/j.neuron.2007.06.019 · Cited by 735 · see citing works
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 · see citing works
Espuny-Camacho, I., Michelsen, K. A., Gall, D., Linaro, D., Hasche, A., Bonnefont, J., Bali, C., Orduz, D., Bilheu, A., Herpoel, A., et al. (2013) · Neuron · doi:10.1016/j.neuron.2012.12.011 · Cited by 568 · see citing works
Modeling human cortical development in vitro using induced pluripotent stem cells
Mariani, J., Simonini, M. V., Palejev, D., Tomasini, L., Coppola, G., Szekely, A. M., Horvath, T. L., & Vaccarino, F. M. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1202944109 · Cited by 526 · 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
NeuN As a Neuronal Nuclear Antigen and Neuron Differentiation Marker
Gusel’nikova, V. V., & Korzhevskiy, D. E. (2015) · Acta Naturae · doi:10.32607/20758251-2015-7-2-42-47 · Cited by 487 · see citing works
Pax6 is a human neuroectoderm cell fate determinant
Zhang, X., Huang, C. T., Chen, J., Pankratz, M. T., Xi, J., Li, J., Yang, Y., LaVaute, T. M., Li, X.-J., Ayala, M., et al. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.04.017 · Cited by 480 · see citing works
RB1 : a prototype tumor suppressor and an enigmaPreprint
Dyson, N. J. (2016) · Genes & Development · doi:10.1101/gad.282145.116 · Cited by 437 · see citing works
Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia
Brennand, K., Savas, J. N., Kim, Y., Tran, N., Simone, A. D., Hashimoto‐Torii, K., Beaumont, K. G., Kim, H., Topol, A., Ladran, I., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.22 · Cited by 406 · see citing works
Sansom, S. N., Griffiths, D. S., Faedo, A., Kleinjan, D., Ruan, Y., Smith, J. C., van Heyningen, V., Rubenstein, J. L. R., & Livesey, F. J. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000511 · Cited by 401 · see citing works
Concise Review: Notch Signaling in Stem Cell Systems
Chiba, S. (2006) · Stem Cells · doi:10.1634/stemcells.2005-0661 · Cited by 400 · see citing works
Transcriptional repression by REST: recruitment of Sin3A and histone deacetylase to neuronal genes
Huang, Y., Myers, S. J., & Dingledine, R. J. (1999) · Nature Neuroscience · doi:10.1038/13165 · Cited by 397 · see citing works
Regulation of Dendritic Development by Neuron-Specific Chromatin Remodeling Complexes
Wu, J. I., Lessard, J. A., Olave, I. A., Qiu, Z., Ghosh, A., Graef, I. A., & Crabtree, G. R. (2007) · Neuron · doi:10.1016/j.neuron.2007.08.021 · Cited by 387 · see citing works
Self-citationChromatin-Remodeling Components of the BAF Complex Facilitate Reprogramming
Singhal, N., Graumann, J., Wu, G., Araúzo-Bravo, M. J., Han, D. W., Greber, B., Gentile, L., Mann, M., & Schöler, H. R. (2010) · Cell · doi:10.1016/j.cell.2010.04.037 · Cited by 378 · cited 2× · see citing works
“generation of mouse iPSCs and their characterization were described previously (Singhal et al., 2010).”
BackgroundMethodSelf-citationSox9 and NFIA coordinate a transcriptional regulatory cascade during the initiation of gliogenesis
Kang, P., Lee, H. K., Glasgow, S. M., Finley, M., Donti, T., Gaber, Z. B., Graham, B. H., Foster, A. E., Novitch, B. G., Gronostajski, R. M., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.01.024 · Cited by 373 · see citing works
Neural stem and progenitor cells shorten S-phase on commitment to neuron production
Arai, Y., Pulvers, J. N., Haffner, C., Schilling, B., Nüsslein, I., Calegari, F., & Huttner, W. Β. (2011) · Nature Communications · doi:10.1038/ncomms1155 · Cited by 372 · see citing works
Trisomy 21 consistently activates the interferon response
Sullivan, K. D., Lewis, H. C., Hill, A. A., Pandey, A., Jackson, L. P., Cabral, J. M., Smith, K. P., Liggett, L. A., Gomez, E. B., Galbraith, M. D., et al. (2016) · eLife · doi:10.7554/elife.16220 · Cited by 362 · see citing works
Translating Dosage Compensation to Trisomy 21
Jiang, J., Jing, Y.-C., Cost, G., Chiang, J.-C., Kolpa, H. J., Cotton, A. M., Carone, D. M., Carone, B. R., Shivak, D. A., Guschin, D., et al. (2013) · Nature · doi:10.1038/nature12394 · Cited by 349 · see citing works
Wnt-mediated self-renewal of neural stem/progenitor cells
Kalani, M. Y. S., Cheshier, S. H., Cord, B. J., Bababeygy, S. R., Vogel, H. S., Weissman, I. L., Palmer, T. D., & Nusse, R. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808616105 · Cited by 333 · see citing works
Domains of genome-wide gene expression dysregulation in Down’s syndrome
Letourneau, A., Santoni, F. A., Bonilla, X., Sailani, M. R., Gonzalez, D., Kind, J., Chevalier, C., Thurman, R., Sandstrom, R. S., Hibaoui, Y., et al. (2014) · Nature · doi:10.1038/nature13200 · Cited by 319 · see citing works
A Human Stem Cell Model of Early Alzheimer’s Disease Pathology in Down Syndrome
Shi, Y., Kirwan, P., Smith, J., MacLean, G., Orkin, S. H., & Livesey, F. J. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003771 · Cited by 310 · see citing works
(1993) · PubMed · Cited by 301 · see citing works
Wisniewski, K. E. (2005) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320370755 · Cited by 297 · see citing works
IFNγ signaling—Does it mean JAK–STAT?
Gough, D. J., Levy, D. E., Johnstone, R. W., & Clarke, C. J. (2008) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2008.08.004 · Cited by 290 · 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
Guidi, S., Bonasoni, P., Ceccarelli, C., Santini, D., Gualtieri, F., Ciani, E., & Bartesaghi, R. (2008) · Brain Pathology · doi:10.1111/j.1750-3639.2007.00113.x · Cited by 276 · see citing works
Olig1 and Olig2 triplication causes developmental brain defects in down syndrome.
Chakrabarti, L., Best, T. K., Cramer, N. P., Carney, R. S. E., Isaac, J. T. R., Galdzicki, Z., & Haydar, T. F. (2010) · Nature Neuroscience · doi:10.1038/nn.2600 · Cited by 258 · see citing works
Nishitani, H., Taraviras, S. L., Lygerou, Z., & Nishimoto, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105406200 · Cited by 254 · see citing works
Ciernia, A. V., Matheos, D. P., Barrett, R. M., Kramár, E. A., Azzawi, S., Chen, Y., Magnan, C. N., Zeller, M. D., Sylvain, A. S., Häettig, J., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3359 · Cited by 234 · see citing works
Verheijen, R., Kuijpers, H. J. H., Schlingemann, R. O., Boehmer, A. L. M., DRIEL, R. V., Brakenhoff, G. J., & Ramaekers, F. C. S. (1989) · Journal of Cell Science · doi:10.1242/jcs.92.1.123 · Cited by 222 · 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
Ninkovic, J., Steiner-Mezzadri, A., Jawerka, M., Akinci, U., Masserdotti, G., Petricca, S., Fischer, J., von Holst, A., Beckers, J., Lie, D. C., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.07.002 · Cited by 208 · see citing works
Deficits in human trisomy 21 iPSCs and neurons
Weick, J. P., Held, D. L., Bonadurer, G. F., Doers, M. E., Liu, Y., Maguire, C., Clark, A., Knackert, J. A., Molinarolo, K., Musser, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1216575110 · Cited by 205 · see citing works
Trisomy 21 and early brain development
Haydar, T. F., & Reeves, R. H. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2011.11.001 · Cited by 200 · see citing works
Chakrabarti, L., Galdzicki, Z., & Haydar, T. F. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3406-07.2007 · Cited by 199 · see citing works
Rodent models in Down syndrome research: impact and future opportunities
Hérault, Y., Delabar, J. M., Fisher, E., Tybulewicz, V. L. J., Yu, E. Y., & Brault, V. (2017) · Disease Models & Mechanisms · doi:10.1242/dmm.029728 · Cited by 191 · see citing works
AF10 Regulates Progressive H3K79 Methylation and HOX Gene Expression in Diverse AML Subtypes
Deshpande, A., Deshpande, A., Sinha, A., Chen, L., Chang, J., Cihan, A., Fazio, M., Chen, C., Zhu, N., Koche, R., et al. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.10.009 · Cited by 172 · see citing works
Self-citationHibaoui, Y., Grad, I., Letourneau, A., Sailani, M. R., Dahoun, S., Santoni, F. A., Gimelli, S., Guipponi, M., Pelte, M. F., Béna, F., et al. (2014) · EMBO Molecular Medicine · doi:10.1002/emmm.201302848 · Cited by 170 · see citing works
Mouse models of Down syndrome: gene content and consequences
Gupta, M., Dhanasekaran, A. R., & Gardiner, K. (2016) · Mammalian Genome · doi:10.1007/s00335-016-9661-8 · Cited by 167 · see citing works
Regulation of cerebral cortical neurogenesis by the Pax6 transcription factor
Manuel, M. N., Mi, D., Mason, J. O., & Price, D. J. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00070 · Cited by 153 · see citing works
Maclean, G., Menne, T., Guo, G., Sanchez, D. J., Park, I.-H., Daley, G., & Orkin, S. (2011) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1215468109 · Cited by 153 · see citing works
Briggs, J. A., Sun, J., Shepherd, J., Ovchinnikov, D. A., Chung, T.-L., Nayler, S. P., Kao, L.-P., Morrow, C. A., Thakar, N. Y., Soo, S.-Y., et al. (2013) · Stem Cells · doi:10.1002/stem.1297 · Cited by 151 · see citing works
Generation of cortical neurons from mouse embryonic stem cells
Gaspard, N., Bouschet, T., Herpoel, A., Naeije, G., van den Ameele, J., & Vanderhaeghen, P. (2009) · Nature Protocols · doi:10.1038/nprot.2009.157 · Cited by 142 · see citing works
Hämmerle, B., Ulin, E., Guimera, J., Becker, W., Guillemot, F., & Tejedor, F. J. (2011) · Development · doi:10.1242/dev.066167 · Cited by 137 · see citing works
Faizi, M., Bader, P. L., Tun, C., Encarnacion, A., Kleschevnikov, A. M., Belichenko, P. V., Saw, N. L., Priestley, M., Tsien, R. W., Mobley, W. C., et al. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.04.011 · Cited by 134 · see citing works
Usp16 contributes to somatic stem-cell defects in Down’s syndrome
Adorno, M., Sikandar, S. S., Mitra, S. S., Kuo, A. H., di Robilant, B. N., Acosta, V. H., Ouadah, Y., Quarta, M., Rodriguez, J., Qian, D., et al. (2013) · Nature · doi:10.1038/nature12530 · Cited by 134 · see citing works
Glutamate as a Modulator of Embryonic and Adult Neurogenesis
Schlett, K. (2006) · Current Topics in Medicinal Chemistry · doi:10.2174/156802606777323665 · Cited by 131 · see citing works
Alexandrow, M. G., & Hamlin, J. L. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200409055 · Cited by 131 · see citing works
Lane, A. A., Chapuy, B., Lin, C. Y., Tivey, T. R., Li, H., Townsend, E. C., van Bodegom, D., Day, T. A., Wu, S.-C., Liu, H., et al. (2014) · Nature Genetics · doi:10.1038/ng.2949 · Cited by 127 · see citing works
Kazuki, Y., Gao, F. J., Li, Y., Moyer, A. J., Devenney, B., Hiramatsu, K., Miyagawa-Tomita, S., Abe, S., Kazuki, K., Kajitani, N., et al. (2020) · eLife · doi:10.7554/elife.56223 · Cited by 125 · cited 1× · see citing works
“In addition to the development of newer mouse models (Kazuki et al., 2020), human-induced pluripotent stem cells (hiPSCs) (Takahashi and Yamanaka, 2006) (Takahashi et al.”
BackgroundLuk, K. C., Kennedy, T. E., & Sadikot, A. F. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-06-02239.2003 · Cited by 124 · see citing works
Aziz, N. M., Guedj, F., Pennings, J. L. A., Olmos-Serrano, J. L., Siegel, A., Haydar, T. F., & Bianchi, D. W. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.031013 · Cited by 118 · see citing works
E2F8 contributes to human hepatocellular carcinoma via regulating cell proliferation.
Deng, Q., Wang, Q., Zong, W., Zheng, D.-L., Wen, Y., Wang, K.-S., Teng, X.-M., Zhang, X., Huang, J., & Han, Z.-G. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-3082 · Cited by 111 · see citing works
Aneuploidy Causes Non-genetic Individuality
Beach, R. R., Ricci-Tam, C., Brennan, C. M., Moomau, C. A., Hsu, P.-H., Hua, B., Silberman, R. E., Springer, M., & Amon, A. (2017) · Cell · doi:10.1016/j.cell.2017.03.021 · Cited by 109 · see citing works
Rouhani, F. J., Zou, X., Danecek, P., Badja, C., Amarante, T. D., Koh, G., Wu, Q., Memari, Y., Durbin, R., Martincorena, I., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01147-3 · Cited by 105 · cited 2× · see citing works
“…results for impaired neurogenesis in DS, perhaps due to a lack of standardized in vitro neural differentiation protocols (Shi et al., 2012; Briggs et al., 2013; Lu et al., 2013; Weick et al., 2013; Hibaoui et al., 2014; Sobol et al., 2019) or variations in hiPSC lines (Rouhani et al., 2022).”
BackgroundHyperkalemia 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
The use of mouse models to understand and improve cognitive deficits in Down syndrome
Das, I., & Reeves, R. H. (2011) · Disease Models & Mechanisms · doi:10.1242/dmm.007716 · Cited by 99 · see citing works
Integrative Analysis of ChIP-Chip and ChIP-Seq Dataset
Zhu, L. J. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-607-8_8 · Cited by 96 · 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
“We found reduced neural differentiation of mouse and human DS stem cells; findings were consistent with mouse and human brain studies (Contestabile et al., 2007; Larsen et al., 2008) and in vitro studies using brain-derived human neural progenitors (Bhattacharyya et al.”
ResultUchida, F., Uzawa, K., Kasamatsu, A., Takatori, H., Sakamoto, Y., Ogawara, K., Shiiba, M., Tanzawa, H., & Bukawa, H. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-321 · 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
Lu, H.-E., Yang, Y.-C., Chen, S.-M., Su, H.-L., Huang, P.-C., Tsai, M.-S., Wang, T.-H., Tseng, C.-P., & Hwang, S.-M. (2013) · Experimental Cell Research · doi:10.1016/j.yexcr.2012.09.017 · Cited by 74 · see citing works
Consequences of Trisomy 16 for Mouse Brain Development: Corticogenesis in a Model of Down Syndrome
Haydar, T. F., Blue, M. E., Molliver, M. E., Krueger, B. K., & Yarowsky, P. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-19-06175.1996 · Cited by 66 · see citing works
Cdk2 Inhibition Prolongs G1 Phase Progression in Mouse Embryonic Stem Cells
Koledova, Z. S., Kafkova, L. R., Calabkova, L., Kryštof, V., Doležel, P., & Divoký, V. (2009) · Stem Cells and Development · doi:10.1089/scd.2009.0065 · Cited by 65 · see citing works
Contestabile, A., Fila, T., Bartesaghi, R., & Ciani, E. (2008) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00168.x · Cited by 63 · see citing works
Sobol, M., Klar, J., Laan, L., Shahsavani, M., Schuster, J., Annerén, G., Konzer, A., Mi, J., Bergquist, J., Nordlund, J., et al. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-1585-3 · Cited by 58 · see citing works
Silencing Trisomy 21 with XIST in Neural Stem Cells Promotes Neuronal Differentiation
Czerminski, J. T., & Lawrence, J. (2020) · Developmental Cell · doi:10.1016/j.devcel.2019.12.015 · Cited by 58 · see citing works
Increased dosage of DYRK1A and DSCR1 delays neuronal differentiation in neocortical progenitor cellsPreprint
Kurabayashi, N., & Sanada, K. (2013) · Genes & Development · doi:10.1101/gad.226381.113 · Cited by 57 · see citing works
(2011) · PubMed · Cited by 57 · see citing works
cdk6 Can Shorten G1 Phase Dependent upon the N-terminal INK4 Interaction Domain
Grossel, M. J., Baker, G. L., & Hinds, P. W. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.42.29960 · Cited by 56 · see citing works
Mouse Models for Down Syndrome-Associated Developmental Cognitive Disabilities
Liu, C., Belichenko, P. V., Zhang, L., Fu, D., Kleschevnikov, A. M., Baldini, A., Antonarakis, S. E., Mobley, W. C., & Yu, Y. E. (2011) · Developmental Neuroscience · doi:10.1159/000329422 · Cited by 55 · see citing works
Geminin Regulates Cortical Progenitor Proliferation and Differentiation
Σπέλλα, Μ., Kyrousi, C., Kritikou, E., Σταθοπούλου, Α., Guillemot, F., Kioussis, D., Pachnis, V., Lygerou, Z., & Taraviras, S. L. (2011) · Stem Cells · doi:10.1002/stem.678 · Cited by 50 · 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
Song, M., Mohamad, O., Chen, D., & Yu, S. P. (2012) · Stem Cells and Development · doi:10.1089/scd.2012.0556 · Cited by 40 · see citing works
Both cdc2 and cdk2 promote S phase initiation in Xenopus egg extracts
Chevalier, S., Tassan, J., Cox, R., Philippe, M., & Ford, C. (1995) · Journal of Cell Science · doi:10.1242/jcs.108.5.1831 · Cited by 39 · see citing works
Katreddi, R. R., Taroc, E. Z. M., Hicks, S. M., Lin, J. M., Liu, S., Xiang, M., & Forni, P. E. (2022) · Development · doi:10.1242/dev.200448 · Cited by 37 · see citing works
Castro, B. D., Pardal, R., García‐Flores, P., Sobrino, V., Durán, R., Piruat, J. I., & López‐Barneo, J. (2015) · EMBO Reports · doi:10.15252/embr.201540982 · Cited by 36 · see citing works
Questioned validity of Gene Expression Dysregulated Domains in Down's Syndrome
Do, L. H., Mobley, W. C., & Singhal, N. (2015) · F1000Research · doi:10.12688/f1000research.6735.1 · Cited by 17 · see citing works
Self-citationBAF Complex Enhances Reprogramming of Adult Human Fibroblasts
Singhal, N., & Araúzo-Bravo, M. J. (2016) · Journal of Stem Cell Research & Therapy · doi:10.4172/2157-7633.1000336 · Cited by 7 · see citing works
Self-citationSharma, V., Nehra, S., & Singhal, N. (2022) · Stem Cell Research · doi:10.1016/j.scr.2022.102890 · Cited by 6 · see citing works
Self-citationNehra, S., Sharma, V., Singh, M., Singhal, P., & Singhal, N. (2022) · Stem Cell Research · doi:10.1016/j.scr.2022.102771 · Cited by 5 · see citing works
Self-citation
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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
“…come from iPSC modelling, in which NPCs that are specified spatially (for example, dorsal versus ventral) and temporally (for example, early born versus late born) can be used to analyse neurogenesis across development 65,70–78 and to model aspects of neurogenesis thought to occur in vivo in DS.”
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
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
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
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
Atak, Z., Srivastava, A., Gandhi, S., Park, E., Williams, J., Torii, M., & Haydar, T. F. (2025) · Journal of Neuroscience · doi:10.1523/jneurosci.0040-25.2025 · Cited by 2 · see citing works
Nehra, S., Sharma, V., Umrani, M. R., & Singhal, N. (2023) · Stem Cell Research · doi:10.1016/j.scr.2023.103041 · Cited by 2 · see citing works
Self-citationIn Vitro Modeling of Down Syndrome Neurogenesis Using Human-Induced Pluripotent Stem Cells
Sharma, V., Chhawari, H., Joshi, P., Nehra, S., & Singhal, N. (2025) · Journal of Visualized Experiments · doi:10.3791/67382 · Cited by 1 · see citing works
Self-citationREST 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
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
Azieva, A. M., Vasilyeva, T. A., Maksimenko, O. G., Davydenko, K., Зинченко, Р. А., & Владимирович, М. А. (2026) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-026-01692-z
Larsen, E. C., Moon, J. E., King, O. D., & Lawrence, J. B. (2026) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2026.02.014
Aberrant 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
Castroflorio, E., Cabot, J., Suau, M., Santillan, A. J., Gomez, G. V., Fernández‐García, P., Lladó, V., Escribá, P. V., & Torres, M. (2026) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2026.120021
- Authors
- Sharma, V., Nehra, S., Do, L. H., Ghosh, A., Deshpande, A. J., & Singhal, N.
- Affiliations
- National Centre for Cell Science (IN)
- University of California San Diego (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Singhal, Nishant
- Venue
- Frontiers in Genetics
- Publisher
- Frontiers Media SA
- Published
- 2022-10-12
- Volume
- 13
- Pages
- 1007519-1007519
- ISSN
- 1664-8021 (ISSN-L)
- PMC
- PMC9596798
- OpenAlex
- W4304786046
- Cited by
- 14
- References
- 106
- Citations by year
- 2026: 7 · 2025: 2 · 2024: 3 · 2023: 2
- FWCI
- 0.64
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Genetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Centre for Cell Science
- 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 › Developmental Biology and Gene Regulation
- Keywords
- Down syndrome, cell cycle dysregulation, neural progenitor proliferation, Pax6, BAF chromatin remodeling complex, rest, Notch signaling, Wnt signaling, interferon signaling, NFIB, POU3F4, cortical lamination
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