Single-cell analysis of prenatal and postnatal human cortical development
成果类型：
Article
署名作者：
Velmeshev, Dmitry; Perez, Yonatan; Yan, Zihan; Valencia, Jonathan E.; Castaneda-Castellanos, David R.; Wang, Li; Schirmer, Lucas; Mayer, Simone; Wick, Brittney; Wang, Shaohui; Nowakowski, Tomasz Jan; Paredes, Mercedes; Huang, Eric J.; Kriegstein, Arnold R.
署名单位：
University of California System; University of California San Francisco; University of California System; University of California San Francisco; Duke University; Ruprecht Karls University Heidelberg; Ruprecht Karls University Heidelberg; Ruprecht Karls University Heidelberg; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; Ruprecht Karls University Heidelberg; University of California System; University of California Santa Cruz; University of California System; University of California San Francisco; University of California System; University of California San Francisco
刊物名称：
SCIENCE
ISSN/ISSBN：
0036-12502
DOI：
10.1126/science.adf0834
发表日期：
2023-10-13
页码：
173-+
关键词：
摘要：
We analyzed >700,000 single-nucleus RNA sequencing profiles from 106 donors during prenatal and postnatal developmental stages and identified lineage-specific programs that underlie the development of specific subtypes of excitatory cortical neurons, interneurons, glial cell types, and brain vasculature. By leveraging single-nucleus chromatin accessibility data, we delineated enhancer gene regulatory networks and transcription factors that control commitment of specific cortical lineages. By intersecting our results with genetic risk factors for human brain diseases, we identified the cortical cell types and lineages most vulnerable to genetic insults of different brain disorders, especially autism. We find that lineage-specific gene expression programs up-regulated in female cells are especially enriched for the genetic risk factors of autism. Our study captures the molecular progression of cortical lineages across human development.