A Single-Cell Transcriptomic Atlas of Human Neocortical Development during Mid-gestation
| Autor: | William E. Lowry, Daniel H. Geschwind, Jennifer K. Lowe, Elizabeth K. Ruzzo, Carli K. Opland, Melinda Gevorgian, Tarik Hadzic, William Connell, Jason L. Stein, Susanne Nichterwitz, Andrew G. Elkins, Flora I. Hinz, Daning Lu, Kathrin Plath, Xu Shi, Mark Gerstein, Justin Langerman, Celine K. Vuong, Shan Sabri, Damon Polioudakis, Luis de la Torre-Ubieta |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cell type Autism Spectrum Disorder Neurogenesis Ependymoglial Cells Cell Gestational Age Neocortex Cell fate determination Biology Article Transcriptome 03 medical and health sciences 0302 clinical medicine Neural Stem Cells Interneurons Pregnancy Intellectual Disability Subplate Databases Genetic medicine Humans Gene Regulatory Networks RNA-Seq Telophase Gene Transcription factor Cerebral Cortex Neurons Epilepsy Gene Expression Profiling General Neuroscience Cell Cycle Gene Expression Regulation Developmental 030104 developmental biology medicine.anatomical_structure Pregnancy Trimester Second Female Single-Cell Analysis Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Neuron |
| ISSN: | 0896-6273 |
| Popis: | We performed RNA sequencing on 40,000 cells to create a high-resolution single-cell gene expres-sion atlas of developing human cortex, providing the first single-cell characterization of previously uncharacterized cell types, including human sub-plate neurons, comparisons with bulk tissue, and systematic analyses of technical factors. These data permit deconvolution of regulatory networks connecting regulatory elements and transcriptional drivers to single-cell gene expression programs, significantly extending our understanding of human neurogenesis, cortical evolution, and the cellular basis of neuropsychiatric disease. We tie cell-cycle progression with early cell fate decisions during neurogenesis, demonstrating that differentiation occurs on a transcriptomic continuum; rather than only expressing a few transcription factors that drive cell fates, differentiating cells express broad, mixed cell-type transcriptomes before telophase. By mapping neuropsychiatric disease genes to cell types, we implicate dysregulation of specific cell types in ASD, ID, and epilepsy. We developed CoDEx, an online portal to facilitate data access and browsing. |
| Databáze: | OpenAIRE |
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