研究人员分析了106个供体在产前和产后发育阶段的700000个单核RNA测序图谱，并确定了谱系特异性程序，这些程序是兴奋性皮质神经元、中间神经元、胶质细胞类型和脑血管系统特定亚型发育的基础。通过利用单核染色质可及性数据，研究人员描绘了控制特定皮质谱系的增强基因调控网络和转录因子。
通过将这些研究结果与人类脑部疾病的遗传风险因素相结合，研究人员人员确定了最容易受到不同脑部疾病（尤其是自闭症）遗传损害的皮层细胞类型和谱系。
研究人员发现，谱系特异性基因表达程序在女性细胞中上调，尤其丰富了自闭症的遗传风险因素。这项研究捕捉到了整个人类发育过程中皮层谱系的分子进展。
附：英文原文
Title: Single-cell analysis of prenatal and postnatal human cortical development
Author: Dmitry Velmeshev, Yonatan Perez, Zihan Yan, Jonathan E. Valencia, David R. Castaneda-Castellanos, Li Wang, Lucas Schirmer, Simone Mayer, Brittney Wick, Shaohui Wang, Tomasz Jan Nowakowski, Mercedes Paredes, Eric J. Huang, Arnold R. Kriegstein
Issue&Volume: 2023-10-13
Abstract: 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.
DOI: adf0834
Source: https://www.science.org/doi/10.1126/science.adf0834