北京大学何爱彬研究组开发出新技术实现更高维度的表观基因组重建。这一研究成果于2021年5月6日在线发表在国际学术期刊《自然—方法学》上。

研究人员开发了CoTECH，这是一种组合式条形码方法，可实现染色质占据和转录组的高通量单细胞联合检测。研究人员使用CoTECH来测试了二价组蛋白标记（H3K4me3和H3K27me3），以及从初始到活化的小鼠胚胎干细胞转录。研究人员还使用转录组来解析伪时态双价轨迹，并破解了H3K4me3/H3K27me3与转录水平之间特定的相互作用，从而在伪单细胞中获得并存的二价标记。

接下来，研究人员揭示了在两波造血细胞中内皮细胞向造血细胞过渡的调控基础，以及指导造血内皮细胞出现的独特增强子-基因连接框架，这表明造血干细胞活化的转录调控具有独特的表观遗传控制。CoTECH为染色质占据和转录的单细胞共分析提供了有效的框架，从而实现了更高维度的表观基因组重建。

据介绍，细胞命运决定中的解密机制需要在转录调控中多维表观基因组状态的单细胞整体重建。

附：英文原文

Title: Single-cell joint detection of chromatin occupancy and transcriptome enables higher-dimensional epigenomic reconstructions

Author: Haiqing Xiong, Yingjie Luo, Qianhao Wang, Xianhong Yu, Aibin He

Issue&Volume: 2021-05-06

Abstract: Deciphering mechanisms in cell-fate decisions requires single-cell holistic reconstructions of multidimensional epigenomic states in transcriptional regulation. Here we develop CoTECH, a combinatorial barcoding method allowing high-throughput single-cell joint detection of chromatin occupancy and transcriptome. We used CoTECH to examine bivalent histone marks (H3K4me3 and H3K27me3) with transcription from naive to primed mouse embryonic stem cells. We also derived concurrent bivalent marks in pseudosingle cells using transcriptome as an anchor for resolving pseudotemporal bivalency trajectories and disentangling a context-specific interplay between H3K4me3/H3K27me3 and transcription level. Next, we revealed the regulatory basis of endothelial-to-hematopoietic transition in two waves of hematopoietic cells and distinctive enhancer-gene-linking schemes guiding hemogenic endothelial cell emergence, indicating a unique epigenetic control of transcriptional regulation for hematopoietic stem cell priming. CoTECH provides an efficient framework for single-cell coassay of chromatin occupancy and transcription, thus enabling higher-dimensional epigenomic reconstructions. 

DOI: 10.1038/s41592-021-01129-z

Source: https://www.nature.com/articles/s41592-021-01129-z