Author:
Tian Wei,Zhou Jingtian,Bartlett Anna,Zeng Qiurui,Liu Hanqing,Castanon Rosa G.,Kenworthy Mia,Altshul Jordan,Valadon Cynthia,Aldridge Andrew,Nery Joseph R.,Chen Huaming,Xu Jiaying,Johnson Nicholas D.,Lucero Jacinta,Osteen Julia K.,Emerson Nora,Rink Jon,Lee Jasper,Li Yang,Siletti Kimberly,Liem Michelle,Claffey Naomi,O’Connor Caz,Yanny Anna Marie,Nyhus Julie,Dee Nick,Casper Tamara,Shapovalova Nadiya,Hirschstein Daniel,Hodge Rebecca,Levi Boaz P.,Keene C. Dirk,Linnarsson Sten,Lein Ed,Ren Bing,Behrens M. Margarita,Ecker Joseph R.
Abstract
Delineating the gene regulatory programs underlying complex cell types is fundamental for understanding brain functions in health and disease. Here, we comprehensively examine human brain cell epigenomes by probing DNA methylation and chromatin conformation at single-cell resolution in over 500,000 cells from 46 brain regions. We identified 188 cell types and characterized their molecular signatures. Integrative analyses revealed concordant changes in DNA methylation, chromatin accessibility, chromatin organization, and gene expression across cell types, cortical areas, and basal ganglia structures. With these resources, we developed scMCodes that reliably predict brain cell types using their methylation status at select genomic sites. This multimodal epigenomic brain cell atlas provides new insights into the complexity of cell type-specific gene regulation in the adult human brain.
Publisher
Cold Spring Harbor Laboratory