美国西奈山伊坎医学院Panos Roussos研究小组揭示了多组单细胞谱识别出产后大脑的关键调节因子。相关论文于2025年2月17日发表在《自然—遗传学》杂志上。

为了促进他们对出生后大脑发育的理解，该课题组人员同时分析了来自10个供体大脑区域的101924个单核的基因表达和染色质可及性，涵盖了从婴儿期到成年后期的五个关键出生阶段。利用该数据集和染色体构象捕获数据，小组构建了基于增强子的基因调控网络，以鉴定大脑发育的细胞类型特异性调控因子，并解释十种主要大脑疾病的全基因组关联研究位点。

他们的分析将2318个细胞特异性位点与1149个独特基因联系起来，代表了与所研究性状相关的41%的位点，并强调了55个影响几种疾病表型的基因。伪时间分析揭示了出生后少突发生的不同阶段及其调控程序。这些发现为出生后大脑发育关键时间点的细胞类型特异性基因调控提供了一个全面的数据集。

据介绍，人类大脑的发育跨越了从胚胎发育到成年的过程，其动态基因表达受细胞类型特异性顺式调控元件活性和三维基因组组织的控制。

附：英文原文

Title: Multiomic single-cell profiling identifies critical regulators of postnatal brain

Author: Clarence, Tereza, Bendl, Jaroslav, Cao, Xuan, Wang, Xinyi, Zheng, Shiwei, Hoffman, Gabriel E., Kozlenkov, Alexey, Hong, Aram, Iskhakova, Marina, Jaiswal, Manoj K., Murphy, Sarah, Yu, Alexander, Haroutunian, Vahram, Dracheva, Stella, Akbarian, Schahram, Fullard, John F., Yuan, Guo-Cheng, Lee, Donghoon, Roussos, Panos

Issue&Volume: 2025-02-17

Abstract: Human brain development spans from embryogenesis to adulthood, with dynamic gene expression controlled by cell-type-specific cis-regulatory element activity and three-dimensional genome organization. To advance our understanding of postnatal brain development, we simultaneously profiled gene expression and chromatin accessibility in 101,924 single nuclei from four brain regions across ten donors, covering five key postnatal stages from infancy to late adulthood. Using this dataset and chromosome conformation capture data, we constructed enhancer-based gene regulatory networks to identify cell-type-specific regulators of brain development and interpret genome-wide association study loci for ten main brain disorders. Our analysis connected 2,318 cell-specific loci to 1,149 unique genes, representing 41% of loci linked to the investigated traits, and highlighted 55 genes influencing several disease phenotypes. Pseudotime analysis revealed distinct stages of postnatal oligodendrogenesis and their regulatory programs. These findings provide a comprehensive dataset of cell-type-specific gene regulation at critical timepoints in postnatal brain development.

DOI: 10.1038/s41588-025-02083-8

Source: https://www.nature.com/articles/s41588-025-02083-8