生物
染色质
造血
祖细胞
RNA序列
表观遗传学
干细胞
转录因子
转录组
细胞生物学
计算生物学
背景(考古学)
遗传学
基因
细胞分化
基因表达
古生物学
作者
Anna Maria Ranzoni,Andrea Tangherloni,Ivan Berest,Simone G. Riva,Brynelle Myers,Paulina M. Strzelecka,Jiarui Xu,Elisa Panada,Irina Mohorianu,Judith B. Zaugg,Ana Cvejic
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2021-03-01
卷期号:28 (3): 472-487.e7
被引量:175
标识
DOI:10.1016/j.stem.2020.11.015
摘要
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.
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