英国剑桥大学CambridgAna Cvejic研究组取得一项新突破。他们对人类发育过程中造血功能进行了整合单细胞RNA测序（scRNA-seq）和转座酶可及的染色质测序（scATAC-seq）分析。这一研究成果发表在2020年12月21日出版的国际学术期刊《细胞-干细胞》杂志上。

他们将scRNA-seq和单细胞分析应用于scATAC-seq，用于研究来自胎儿肝和骨髓的8,000多个人类免疫表型血细胞。他们推断这些血细胞的分化轨迹，并鉴定了造血干细胞（HSC）/多能祖细胞（MPP）下游的三个高度增殖的寡能祖细胞。沿着这一轨迹，他们观察到了染色质可及性和分化的相反模式，这与不同谱系特异性转录因子活性的动态变化相吻合。

染色质可及性和基因表达的综合分析显示，在HSCs / MPPs传承之前，它们具有广泛的表观遗传性，但没有转录启动。最后，他们对HSC / MPP的分类方法进行了完善和功能验证，并实现了大约90％的富集。他们的研究为血液病理学和再生医学背景下的人类发育性造血功能的未来研究提供了有用的框架。

研究人员表示，在人类发育过程中对造血功能的调节仍不清楚。

附：英文原文

Title: Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Human Developmental Hematopoiesis

Author: Anna Maria Ranzoni, Andrea Tangherloni, Ivan Berest, Simone Giovanni Riva, Brynelle Myers, Paulina M. Strzelecka, Jiarui Xu, Elisa Panada, Irina Mohorianu, Judith B. Zaugg, Ana Cvejic

Issue&Volume: 2020-12-21

Abstract: Regulation of hematopoiesis during human development remains poorly defined. Here we applied single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to over 8,000 human immunophenotypic blood cells from fetal liver and bone marrow. We inferred their differentiation trajectory and identified three highly proliferative oligopotent progenitor populations downstream of hematopoietic stem cells (HSCs)/multipotent progenitors (MPPs). Along this trajectory, we observed opposing patterns of chromatin accessibility and differentiation that coincided with dynamic changes in the activity of distinct lineage-specific transcription factors. Integrative analysis of chromatin accessibility and gene expression revealed extensive epigenetic but not transcriptional priming of HSCs/MPPs prior to their lineage commitment. Finally, we refined and functionally validated the sorting strategy for the HSCs/MPPs and achieved around 90% enrichment. Our study provides a useful framework for future investigation of human developmental hematopoiesis in the context of blood pathologies and regenerative medicine.

DOI: 10.1016/j.stem.2020.11.015

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30553-1