*Result*: Single-Cell Transcriptome Meta-Analysis Reveals Epigenomic and Chromatin Dysregulation in Developing Neurons Derived From Human ESCs With 1q21.1 CNVs.
Title:
Single-Cell Transcriptome Meta-Analysis Reveals Epigenomic and Chromatin Dysregulation in Developing Neurons Derived From Human ESCs With 1q21.1 CNVs.
Authors:
Torigata K; Department of Physiology and Cell Biology, Kobe University School of Medicine, Kobe, Japan., Nomura J; Department of Physiology and Cell Biology, Kobe University School of Medicine, Kobe, Japan., Takumi T; Department of Physiology and Cell Biology, Kobe University School of Medicine, Kobe, Japan.
Source:
Autism research : official journal of the International Society for Autism Research [Autism Res] 2026 Jan; Vol. 19 (1), pp. e70156. Date of Electronic Publication: 2025 Dec 24.
Publication Type:
Journal Article; Meta-Analysis
Language:
English
Journal Info:
Publisher: John Wiley & Sons, Inc Country of Publication: United States NLM ID: 101461858 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1939-3806 (Electronic) Linking ISSN: 19393806 NLM ISO Abbreviation: Autism Res Subsets: MEDLINE
Imprint Name(s):
Original Publication: Hoboken, NJ : John Wiley & Sons, Inc.
MeSH Terms:
References:
Abrahams, B. S., D. E. Arking, D. B. Campbell, et al. 2013. “SFARI Gene 2.0: A Community‐Driven Knowledgebase for the Autism Spectrum Disorders (ASDs).” Molecular Autism 4, no. 1: 36. https://doi.org/10.1186/2040‐2392‐4‐36.
Alvarez, M. J., Y. Shen, F. M. Giorgi, et al. 2016. “Functional Characterization of Somatic Mutations in Cancer Using Network‐Based Inference of Protein Activity.” Nature Genetics 48, no. 8: 838–847. https://doi.org/10.1038/ng.3593.
Bhattacharya, S., P. Dunn, C. G. Thomas, et al. 2018. “ImmPort, Toward Repurposing of Open Access Immunological Assay Data for Translational and Clinical Research.” Scientific Data 5: 180015. https://doi.org/10.1038/sdata.2018.15.
Blalock, E. M., J. W. Geddes, K. C. Chen, N. M. Porter, W. R. Markesbery, and P. W. Landfield. 2004. “Incipient Alzheimer's Disease: Microarray Correlation Analyses Reveal Major Transcriptional and Tumor Suppressor Responses.” Proceedings of the National Academy of Sciences of the United States of America 101, no. 7: 2173–2178. https://doi.org/10.1073/pnas.0308512100.
Blázquez, A., L. Rodriguez‐Revenga, M. I. Alvarez‐Mora, and R. Calvo. 2025. “Clinical and Genetic Findings in Autism Spectrum Disorders Analyzed Using Exome Sequencing.” Frontiers in Psychiatry 16: 1515793. https://doi.org/10.3389/fpsyt.2025.1515793.
Cao, J., M. Spielmann, X. Qiu, et al. 2019. “The Single‐Cell Transcriptional Landscape of Mammalian Organogenesis.” Nature 566, no. 7745: 496–502. https://doi.org/10.1038/s41586‐019‐0969‐x.
Chen, J., and Z. Guan. 2022. “Function of Oncogene Mycn in Adult Neurogenesis and Oligodendrogenesis.” Molecular Neurobiology 59, no. 1: 77–92. https://doi.org/10.1007/s12035‐021‐02584‐7.
Dall'Aglio, L., T. Muka, C. A. M. Cecil, et al. 2018. “The Role of Epigenetic Modifications in Neurodevelopmental Disorders: A Systematic Review.” Neuroscience and Biobehavioral Reviews 94: 17–30. https://doi.org/10.1016/j.neubiorev.2018.07.011.
De Jonghe, J., J. W. Opzoomer, A. Vilas‐Zornoza, et al. 2024. “scTrends: A Living Review of Commercial Single‐Cell and Spatial Omic Technologies.” Cell Genomics 4, no. 12: 100723. https://doi.org/10.1016/j.xgen.2024.100723.
Emani, P. S., J. J. Liu, D. Clarke, et al. 2024. “Single‐Cell Genomics and Regulatory Networks for 388 Human Brains.” Science 384, no. 6698: eadi5199. https://doi.org/10.1126/science.adi5199.
ENCODE Project Consortium. 2012. “An Integrated Encyclopedia of DNA Elements in the Human Genome.” Nature 489, no. 7414: 57–74. https://doi.org/10.1038/nature11247.
Felipe, I., J. Martínez‐de‐Villarreal, K. Patel, et al. 2024. “BPTF Cooperates With MYCN and MYC to Link Neuroblastoma Cell Cycle Control to Epigenetic Cellular States.” bioRxiv: 2024.02.11579816. https://doi.org/10.1101/2024.02.11.579816.
Fu, J. M., F. K. Satterstrom, M. Peng, et al. 2022. “Rare Coding Variation Provides Insight Into the Genetic Architecture and Phenotypic Context of Autism.” Nature Genetics 54, no. 9: 1320–1331. https://doi.org/10.1038/s41588‐022‐01104‐0.
Gandal, M. J., P. Zhang, E. Hadjimichael, et al. 2018. “Transcriptome‐Wide Isoform‐Level Dysregulation in ASD, Schizophrenia, and Bipolar Disorder.” Science 362, no. 6420: eaat8127. https://doi.org/10.1126/science.aat8127.
Gao, Y., M. B. Aljazi, Y. Wu, and J. He. 2021. “Vorinostat, a Histone Deacetylase Inhibitor, Ameliorates the Sociability and Cognitive Memory in an Ash1L‐Deletion‐Induced ASD/ID Mouse Model.” Neuroscience Letters 764: 136241. https://doi.org/10.1016/j.neulet.2021.136241.
Glinton, K. E., A. C. E. Hurst, K. M. Bowling, et al. 2021. “Phenotypic Expansion of the BPTF‐Related Neurodevelopmental Disorder With Dysmorphic Facies and Distal Limb Anomalies.” American Journal of Medical Genetics. Part A 185, no. 5: 1366–1378. https://doi.org/10.1002/ajmg.a.62102.
He, S., Z. Liu, D. Y. Oh, and C. J. Thiele. 2013. “MYCN and the Epigenome.” Frontiers in Oncology 3: 1. https://doi.org/10.3389/fonc.2013.00001.
Hodes, R. J., and N. Buckholtz. 2016. “Accelerating Medicines Partnership: Alzheimer's Disease (AMP‐AD) Knowledge Portal Aids Alzheimer's Drug Discovery Through Open Data Sharing.” Expert Opinion on Therapeutic Targets 20, no. 4: 389–391. https://doi.org/10.1517/14728222.2016.1135132.
Iurlaro, M., F. Masoni, I. M. Flyamer, et al. 2024. “Systematic Assessment of ISWI Subunits Shows That NURF Creates Local Accessibility for CTCF.” Nature Genetics 56, no. 6: 1203–1212. https://doi.org/10.1038/s41588‐024‐01767‐x.
Kim, S., and M. J. Webster. 2010. “Correlation Analysis Between Genome‐Wide Expression Profiles and Cytoarchitectural Abnormalities in the Prefrontal Cortex of Psychiatric Disorders.” Molecular Psychiatry 15, no. 3: 326–336. https://doi.org/10.1038/mp.2008.99.
Kuehner, J. N., E. C. Bruggeman, Z. Wen, and B. Yao. 2019. “Epigenetic Regulations in Neuropsychiatric Disorders.” Frontiers in Genetics 10: 268. https://doi.org/10.3389/fgene.2019.00268.
Lemée, M. V., M. N. Loviglio, T. Ye, et al. 2025. “Disrupted Transcriptional Networks Regulated by CHD1L During Neurodevelopment Underlie the Mirrored Neuroanatomical and Growth Phenotypes of the 1q21.1 Copy Number Variant.” Nucleic Acids Research 53, no. 18: gkaf934. https://doi.org/10.1093/nar/gkaf934.
Martinelli, P., O. Schaaf, A. Mantoulidis, et al. 2023. “Discovery of a Chemical Probe to Study Implications of BPTF Bromodomain Inhibition in Cellular and In Vivo Experiments.” ChemMedChem 18, no. 6: e202200686. https://doi.org/10.1002/cmdc.202200686.
Nomura, J., M. Mardo, and T. Takumi. 2021. “Molecular Signatures From Multi‐Omics of Autism Spectrum Disorders and Schizophrenia.” Journal of Neurochemistry 159, no. 4: 647–659. https://doi.org/10.1111/jnc.15514.
Nomura, J., A. Zuko, K. Kishimoto, et al. 2025. “ESC Models of Autism With Copy‐Number Variations Reveal Cell‐Type‐Specific Translational Vulnerability.” Cell Genomics 5, no. 6: 100877. https://doi.org/10.1016/j.xgen.2025.100877.
Nomura, Y., J. Nomura, K. Tamada, et al. 2025. “Isogenic Modeling of 1q21.1 Reciprocal CNVs in Human ES Cells Reveals Divergent Neurodevelopmental Trajectories.” Human Molecular Genetics. https://doi.org/10.1093/hmg/ddaf184.
Pagliaro, A., B. Artegiani, and D. Hendriks. 2025. “Emerging Approaches to Enhance Human Brain Organoid Physiology.” Trends in Cell Biology 35: 483–499. https://doi.org/10.1016/j.tcb.2024.12.001.
Qin, L., K. Ma, Z. J. Wang, et al. 2018. “Social Deficits in Shank3‐Deficient Mouse Models of Autism Are Rescued by Histone Deacetylase (HDAC) Inhibition.” Nature Neuroscience 21, no. 4: 564–575. https://doi.org/10.1038/s41593‐018‐0110‐8.
Rath, S., R. Sharma, R. Gupta, et al. 2021. “MitoCarta3.0: An Updated Mitochondrial Proteome Now With Sub‐Organelle Localization and Pathway Annotations.” Nucleic Acids Research 49, no. D1: D1541–D1547. https://doi.org/10.1093/nar/gkaa1011.
Stark, K. L., B. Xu, A. Bagchi, et al. 2008. “Altered Brain microRNA Biogenesis Contributes to Phenotypic Deficits in a 22q11‐Deletion Mouse Model.” Nature Genetics 40, no. 6: 751–760. https://doi.org/10.1038/ng.138.
Subramanian, A., P. Tamayo, V. K. Mootha, et al. 2005. “Gene Set Enrichment Analysis: A Knowledge‐Based Approach for Interpreting Genome‐Wide Expression Profiles.” Proceedings of the National Academy of Sciences of the United States of America 102, no. 43: 15545–15550. https://doi.org/10.1073/pnas.0506580102.
Taliun, D., D. N. Harris, M. D. Kessler, et al. 2021. “Sequencing of 53,831 Diverse Genomes From the NHLBI TOPMed Program.” Nature 590, no. 7845: 290–299. https://doi.org/10.1038/s41586‐021‐03205‐y.
Tamada, K., and T. Takumi. 2025. “Neurodevelopmental Impact of CNV Models in ASD: Recent Advances and Future Directions.” Current Opinion in Neurobiology 92: 103001. https://doi.org/10.1016/j.conb.2025.103001.
The Cancer Genome Atlas Network. 2008. “Comprehensive Genomic Characterization Defines Human Glioblastoma Genes and Core Pathways.” Nature 455, no. 7216: 1061–1068. https://doi.org/10.1038/nature07385.
Urrestizala‐Arenaza, N., S. Cerchio, F. Cavaliere, and C. Magliaro. 2024. “Limitations of Human Brain Organoids to Study Neurodegenerative Diseases: A Manual to Survive.” Frontiers in Cellular Neuroscience 18: 1419526. https://doi.org/10.3389/fncel.2024.1419526.
Villiger, L., J. Joung, L. Koblan, J. Weissman, O. O. Abudayyeh, and J. S. Gootenberg. 2024. “CRISPR Technologies for Genome, Epigenome and Transcriptome Editing.” Nature Reviews. Molecular Cell Biology 25, no. 6: 464–487. https://doi.org/10.1038/s41580‐023‐00697‐6.
Wolock, S. L., R. Lopez, and A. M. Klein. 2019. “Scrublet: Computational Identification of Cell Doublets in Single‐Cell Transcriptomic Data.” Cell Systems 8, no. 4: 281–291.e289. https://doi.org/10.1016/j.cels.2018.11.005.
Yan, Z. 2024. “Targeting Epigenetic Enzymes for Autism Treatment.” Trends in Pharmacological Sciences 45, no. 9: 764–767. https://doi.org/10.1016/j.tips.2024.06.009.
Zapata, G., K. Yan, and D. J. Picketts. 2022. “Generation of a Mouse Model of the Neurodevelopmental Disorder With Dysmorphic Facies and Distal Limb Anomalies Syndrome.” Human Molecular Genetics 31, no. 20: 3405–3421. https://doi.org/10.1093/hmg/ddac119.
Zheng, G. X., J. M. Terry, P. Belgrader, et al. 2017. “Massively Parallel Digital Transcriptional Profiling of Single Cells.” Nature Communications 8: 14049. https://doi.org/10.1038/ncomms14049.
Alvarez, M. J., Y. Shen, F. M. Giorgi, et al. 2016. “Functional Characterization of Somatic Mutations in Cancer Using Network‐Based Inference of Protein Activity.” Nature Genetics 48, no. 8: 838–847. https://doi.org/10.1038/ng.3593.
Bhattacharya, S., P. Dunn, C. G. Thomas, et al. 2018. “ImmPort, Toward Repurposing of Open Access Immunological Assay Data for Translational and Clinical Research.” Scientific Data 5: 180015. https://doi.org/10.1038/sdata.2018.15.
Blalock, E. M., J. W. Geddes, K. C. Chen, N. M. Porter, W. R. Markesbery, and P. W. Landfield. 2004. “Incipient Alzheimer's Disease: Microarray Correlation Analyses Reveal Major Transcriptional and Tumor Suppressor Responses.” Proceedings of the National Academy of Sciences of the United States of America 101, no. 7: 2173–2178. https://doi.org/10.1073/pnas.0308512100.
Blázquez, A., L. Rodriguez‐Revenga, M. I. Alvarez‐Mora, and R. Calvo. 2025. “Clinical and Genetic Findings in Autism Spectrum Disorders Analyzed Using Exome Sequencing.” Frontiers in Psychiatry 16: 1515793. https://doi.org/10.3389/fpsyt.2025.1515793.
Cao, J., M. Spielmann, X. Qiu, et al. 2019. “The Single‐Cell Transcriptional Landscape of Mammalian Organogenesis.” Nature 566, no. 7745: 496–502. https://doi.org/10.1038/s41586‐019‐0969‐x.
Chen, J., and Z. Guan. 2022. “Function of Oncogene Mycn in Adult Neurogenesis and Oligodendrogenesis.” Molecular Neurobiology 59, no. 1: 77–92. https://doi.org/10.1007/s12035‐021‐02584‐7.
Dall'Aglio, L., T. Muka, C. A. M. Cecil, et al. 2018. “The Role of Epigenetic Modifications in Neurodevelopmental Disorders: A Systematic Review.” Neuroscience and Biobehavioral Reviews 94: 17–30. https://doi.org/10.1016/j.neubiorev.2018.07.011.
De Jonghe, J., J. W. Opzoomer, A. Vilas‐Zornoza, et al. 2024. “scTrends: A Living Review of Commercial Single‐Cell and Spatial Omic Technologies.” Cell Genomics 4, no. 12: 100723. https://doi.org/10.1016/j.xgen.2024.100723.
Emani, P. S., J. J. Liu, D. Clarke, et al. 2024. “Single‐Cell Genomics and Regulatory Networks for 388 Human Brains.” Science 384, no. 6698: eadi5199. https://doi.org/10.1126/science.adi5199.
ENCODE Project Consortium. 2012. “An Integrated Encyclopedia of DNA Elements in the Human Genome.” Nature 489, no. 7414: 57–74. https://doi.org/10.1038/nature11247.
Felipe, I., J. Martínez‐de‐Villarreal, K. Patel, et al. 2024. “BPTF Cooperates With MYCN and MYC to Link Neuroblastoma Cell Cycle Control to Epigenetic Cellular States.” bioRxiv: 2024.02.11579816. https://doi.org/10.1101/2024.02.11.579816.
Fu, J. M., F. K. Satterstrom, M. Peng, et al. 2022. “Rare Coding Variation Provides Insight Into the Genetic Architecture and Phenotypic Context of Autism.” Nature Genetics 54, no. 9: 1320–1331. https://doi.org/10.1038/s41588‐022‐01104‐0.
Gandal, M. J., P. Zhang, E. Hadjimichael, et al. 2018. “Transcriptome‐Wide Isoform‐Level Dysregulation in ASD, Schizophrenia, and Bipolar Disorder.” Science 362, no. 6420: eaat8127. https://doi.org/10.1126/science.aat8127.
Gao, Y., M. B. Aljazi, Y. Wu, and J. He. 2021. “Vorinostat, a Histone Deacetylase Inhibitor, Ameliorates the Sociability and Cognitive Memory in an Ash1L‐Deletion‐Induced ASD/ID Mouse Model.” Neuroscience Letters 764: 136241. https://doi.org/10.1016/j.neulet.2021.136241.
Glinton, K. E., A. C. E. Hurst, K. M. Bowling, et al. 2021. “Phenotypic Expansion of the BPTF‐Related Neurodevelopmental Disorder With Dysmorphic Facies and Distal Limb Anomalies.” American Journal of Medical Genetics. Part A 185, no. 5: 1366–1378. https://doi.org/10.1002/ajmg.a.62102.
He, S., Z. Liu, D. Y. Oh, and C. J. Thiele. 2013. “MYCN and the Epigenome.” Frontiers in Oncology 3: 1. https://doi.org/10.3389/fonc.2013.00001.
Hodes, R. J., and N. Buckholtz. 2016. “Accelerating Medicines Partnership: Alzheimer's Disease (AMP‐AD) Knowledge Portal Aids Alzheimer's Drug Discovery Through Open Data Sharing.” Expert Opinion on Therapeutic Targets 20, no. 4: 389–391. https://doi.org/10.1517/14728222.2016.1135132.
Iurlaro, M., F. Masoni, I. M. Flyamer, et al. 2024. “Systematic Assessment of ISWI Subunits Shows That NURF Creates Local Accessibility for CTCF.” Nature Genetics 56, no. 6: 1203–1212. https://doi.org/10.1038/s41588‐024‐01767‐x.
Kim, S., and M. J. Webster. 2010. “Correlation Analysis Between Genome‐Wide Expression Profiles and Cytoarchitectural Abnormalities in the Prefrontal Cortex of Psychiatric Disorders.” Molecular Psychiatry 15, no. 3: 326–336. https://doi.org/10.1038/mp.2008.99.
Kuehner, J. N., E. C. Bruggeman, Z. Wen, and B. Yao. 2019. “Epigenetic Regulations in Neuropsychiatric Disorders.” Frontiers in Genetics 10: 268. https://doi.org/10.3389/fgene.2019.00268.
Lemée, M. V., M. N. Loviglio, T. Ye, et al. 2025. “Disrupted Transcriptional Networks Regulated by CHD1L During Neurodevelopment Underlie the Mirrored Neuroanatomical and Growth Phenotypes of the 1q21.1 Copy Number Variant.” Nucleic Acids Research 53, no. 18: gkaf934. https://doi.org/10.1093/nar/gkaf934.
Martinelli, P., O. Schaaf, A. Mantoulidis, et al. 2023. “Discovery of a Chemical Probe to Study Implications of BPTF Bromodomain Inhibition in Cellular and In Vivo Experiments.” ChemMedChem 18, no. 6: e202200686. https://doi.org/10.1002/cmdc.202200686.
Nomura, J., M. Mardo, and T. Takumi. 2021. “Molecular Signatures From Multi‐Omics of Autism Spectrum Disorders and Schizophrenia.” Journal of Neurochemistry 159, no. 4: 647–659. https://doi.org/10.1111/jnc.15514.
Nomura, J., A. Zuko, K. Kishimoto, et al. 2025. “ESC Models of Autism With Copy‐Number Variations Reveal Cell‐Type‐Specific Translational Vulnerability.” Cell Genomics 5, no. 6: 100877. https://doi.org/10.1016/j.xgen.2025.100877.
Nomura, Y., J. Nomura, K. Tamada, et al. 2025. “Isogenic Modeling of 1q21.1 Reciprocal CNVs in Human ES Cells Reveals Divergent Neurodevelopmental Trajectories.” Human Molecular Genetics. https://doi.org/10.1093/hmg/ddaf184.
Pagliaro, A., B. Artegiani, and D. Hendriks. 2025. “Emerging Approaches to Enhance Human Brain Organoid Physiology.” Trends in Cell Biology 35: 483–499. https://doi.org/10.1016/j.tcb.2024.12.001.
Qin, L., K. Ma, Z. J. Wang, et al. 2018. “Social Deficits in Shank3‐Deficient Mouse Models of Autism Are Rescued by Histone Deacetylase (HDAC) Inhibition.” Nature Neuroscience 21, no. 4: 564–575. https://doi.org/10.1038/s41593‐018‐0110‐8.
Rath, S., R. Sharma, R. Gupta, et al. 2021. “MitoCarta3.0: An Updated Mitochondrial Proteome Now With Sub‐Organelle Localization and Pathway Annotations.” Nucleic Acids Research 49, no. D1: D1541–D1547. https://doi.org/10.1093/nar/gkaa1011.
Stark, K. L., B. Xu, A. Bagchi, et al. 2008. “Altered Brain microRNA Biogenesis Contributes to Phenotypic Deficits in a 22q11‐Deletion Mouse Model.” Nature Genetics 40, no. 6: 751–760. https://doi.org/10.1038/ng.138.
Subramanian, A., P. Tamayo, V. K. Mootha, et al. 2005. “Gene Set Enrichment Analysis: A Knowledge‐Based Approach for Interpreting Genome‐Wide Expression Profiles.” Proceedings of the National Academy of Sciences of the United States of America 102, no. 43: 15545–15550. https://doi.org/10.1073/pnas.0506580102.
Taliun, D., D. N. Harris, M. D. Kessler, et al. 2021. “Sequencing of 53,831 Diverse Genomes From the NHLBI TOPMed Program.” Nature 590, no. 7845: 290–299. https://doi.org/10.1038/s41586‐021‐03205‐y.
Tamada, K., and T. Takumi. 2025. “Neurodevelopmental Impact of CNV Models in ASD: Recent Advances and Future Directions.” Current Opinion in Neurobiology 92: 103001. https://doi.org/10.1016/j.conb.2025.103001.
The Cancer Genome Atlas Network. 2008. “Comprehensive Genomic Characterization Defines Human Glioblastoma Genes and Core Pathways.” Nature 455, no. 7216: 1061–1068. https://doi.org/10.1038/nature07385.
Urrestizala‐Arenaza, N., S. Cerchio, F. Cavaliere, and C. Magliaro. 2024. “Limitations of Human Brain Organoids to Study Neurodegenerative Diseases: A Manual to Survive.” Frontiers in Cellular Neuroscience 18: 1419526. https://doi.org/10.3389/fncel.2024.1419526.
Villiger, L., J. Joung, L. Koblan, J. Weissman, O. O. Abudayyeh, and J. S. Gootenberg. 2024. “CRISPR Technologies for Genome, Epigenome and Transcriptome Editing.” Nature Reviews. Molecular Cell Biology 25, no. 6: 464–487. https://doi.org/10.1038/s41580‐023‐00697‐6.
Wolock, S. L., R. Lopez, and A. M. Klein. 2019. “Scrublet: Computational Identification of Cell Doublets in Single‐Cell Transcriptomic Data.” Cell Systems 8, no. 4: 281–291.e289. https://doi.org/10.1016/j.cels.2018.11.005.
Yan, Z. 2024. “Targeting Epigenetic Enzymes for Autism Treatment.” Trends in Pharmacological Sciences 45, no. 9: 764–767. https://doi.org/10.1016/j.tips.2024.06.009.
Zapata, G., K. Yan, and D. J. Picketts. 2022. “Generation of a Mouse Model of the Neurodevelopmental Disorder With Dysmorphic Facies and Distal Limb Anomalies Syndrome.” Human Molecular Genetics 31, no. 20: 3405–3421. https://doi.org/10.1093/hmg/ddac119.
Zheng, G. X., J. M. Terry, P. Belgrader, et al. 2017. “Massively Parallel Digital Transcriptional Profiling of Single Cells.” Nature Communications 8: 14049. https://doi.org/10.1038/ncomms14049.
Grant Information:
23KK0132 Japan Society for the Promotion of Science; 24H00620 Japan Society for the Promotion of Science; 24H01241 Japan Society for the Promotion of Science; 23H04233 Japan Society for the Promotion of Science; 24K22036 Japan Society for the Promotion of Science; JP21wm0425011 Japan Agency for Medical Research and Development; JPMJPF2018 Japan Science and Technology Agency; JPMJMS2299 Japan Science and Technology Agency; JPMJMS229B Japan Science and Technology Agency; Takeda Science Foundation
Contributed Indexing:
Keywords: chromatin; copy number variation; epigenome; human ES cell; single‐cell transcriptome
Local Abstract: [plain-language-summary] We studied brain cells grown from human stem cells that carry a genetic change linked to autism. Using advanced analysis, we found that this change affects how certain genes are turned on and off, especially those involved in controlling how DNA is packaged. These results may help us better understand how autism and related conditions develop in the brain.
Local Abstract: [plain-language-summary] We studied brain cells grown from human stem cells that carry a genetic change linked to autism. Using advanced analysis, we found that this change affects how certain genes are turned on and off, especially those involved in controlling how DNA is packaged. These results may help us better understand how autism and related conditions develop in the brain.
Substance Nomenclature:
0 (Chromatin)
Entry Date(s):
Date Created: 20251224 Date Completed: 20260129 Latest Revision: 20260130
Update Code:
20260130
DOI:
10.1002/aur.70156
PMID:
41437869
Database:
MEDLINE
*Further Information*
*Recent efforts to construct disease-specific multimodal omics databases at single-cell resolution, along with advances in reconstructive technologies such as brain organoids, have opened up opportunities to elucidate the molecular basis of complex human neuropsychiatric diseases. In this study, we performed a meta-analysis to characterize disease-associated regulatory modules by performing single-cell transcriptome analysis of developing neurons from reciprocal human ESC models of CNV in the distal 1q21.1 region. As a result, we observed significant directional enrichment of a series of genes in neuronal cells associated with autism spectrum disorder (ASD), bipolar disorder, and schizophrenia. Correlation analyses revealed that the disease-associated signature primarily targeted epigenetic regulatory mechanisms. We also identified Bromodomain PHD Finger Transcription Factor (BPTF), a key component of the NURF chromatin remodeling complex, as a potential target responsible for transcriptome changes related to human neuropsychiatric diseases, including ASD. We provide a practical and straightforward analytical workflow for utilizing both public data and in-house single-cell omics data from disease models.
(© 2025 International Society for Autism Research and Wiley Periodicals LLC.)*