美国加州理工学院
组织中不同类型的细胞具有不同的基因表达程序、染色质状态和核结构。为了在小鼠脑组织切片中的数千个单细胞中关联这种多模式信息，研究人员展示了综合空间基因组学，可将数千个基因组位点与RNA和表观遗传标志物同时在单个细胞中成像。研究人员发现，细胞类型特有的关联和核体周围DNA位点的支架组织了核结构，并与不同细胞类型的不同表达水平相关。
在亚基因组水平上，尽管有不同的表观遗传和表达状态，但活跃和不活跃的X染色体在单细胞中访问类似的域结构。这个工作是将单细胞三维核结构、基因表达和表观遗传修饰在局部组织背景下联系起来的一个重要步骤。
附：英文原文
Title: Single-cell nuclear architecture across cell types in the mouse brain
Author: Yodai Takei, Shiwei Zheng, Jina Yun, Sheel Shah, Nico Pierson, Jonathan White, Simone Schindler, Carsten H. Tischbirek, Guo-Cheng Yuan, Long Cai
Issue&Volume: 2021-09-30
Abstract: Diverse cell types in tissues have distinct gene expression programs, chromatin states and nuclear architectures. To correlate such multimodal information across thousands of single cells in mouse brain tissue sections, we demonstrate integrated spatial genomics, imaging thousands of genomic loci along with RNAs and epigenetic markers simultaneously in individual cells. We revealed that cell type–specific association and scaffolding of DNA loci around nuclear bodies organize the nuclear architecture and correlate with differential expression levels in different cell types. At the submegabase level, active and inactive X chromosomes access similar domain structures in single cells despite distinct epigenetic and expression states. Our report represents a major step forward in linking single-cell 3D nuclear architecture, gene expression and epigenetic modifications in native tissue context.
DOI: abj1966
Source: https://www.science.org/doi/10.1126/science.abj1966