Laboratory of Epigenome Biology, Systems Biology Center, NHLBI, NIH, Bethesda, MD, USA.
Nat Rev Genet. 2021 Apr;22(4):235-250. doi: 10.1038/s41576-020-00300-0. Epub 2020 Nov 26.
Single-cell sequencing-based methods for profiling gene transcript levels have revealed substantial heterogeneity in expression levels among morphologically indistinguishable cells. This variability has important functional implications for tissue biology and disease states such as cancer. Mapping of epigenomic information such as chromatin accessibility, nucleosome positioning, histone tail modifications and enhancer-promoter interactions in both bulk-cell and single-cell samples has shown that these characteristics of chromatin state contribute to expression or repression of associated genes. Advances in single-cell epigenomic profiling methods are enabling high-resolution mapping of chromatin states in individual cells. Recent studies using these techniques provide evidence that variations in different aspects of chromatin organization collectively define gene expression heterogeneity among otherwise highly similar cells.
基于单细胞测序的基因转录本水平分析方法揭示了形态上无法区分的细胞之间表达水平的显著异质性。这种可变性对组织生物学和疾病状态（如癌症）具有重要的功能意义。在批量细胞和单细胞样本中对表观基因组信息（如染色质可及性、核小体定位、组蛋白尾部修饰和增强子-启动子相互作用）进行作图表明，这些染色质状态特征有助于相关基因的表达或抑制。单细胞表观基因组分析方法的进展使得在单个细胞中进行染色质状态的高分辨率作图成为可能。最近使用这些技术的研究提供了证据，表明不同方面的染色质组织的变化共同定义了高度相似的细胞之间的基因表达异质性。
