Multiomic single-cell profiling identifies critical regulators of postnatal brain.

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

Ngôn ngữ: eng

Ký hiệu phân loại: 006.35 *Natural language processing

Thông tin xuất bản: United States : Nature genetics , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 184084

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.
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