Integrative epigenomic and transcriptomic analysis reveals the requirement of JUNB for hematopoietic fate induction

Xia Chen, Peiliang Wang, Hui Qiu, Yonglin Zhu, Xingwu Zhang, Yaxuan Zhang, Fuyu Duan, Shuangyuan Ding, Jianying Guo, Yue Huang and Jie Na ()
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Xia Chen: Tsinghua-Peking Center for Life Sciences
Peiliang Wang: Tsinghua University
Hui Qiu: Tsinghua University
Yonglin Zhu: Tsinghua University
Xingwu Zhang: Tsinghua University
Yaxuan Zhang: Tsinghua University
Fuyu Duan: Guangzhou Women and Children’s Medical Center
Shuangyuan Ding: Tsinghua University
Jianying Guo: Peking University Third Hospital
Yue Huang: Chinese Academy of Medical Sciences & Peking Union Medical College
Jie Na: Tsinghua University

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Human pluripotent stem cell differentiation towards hematopoietic progenitor cell can serve as an in vitro model for human embryonic hematopoiesis, but the dynamic change of epigenome and transcriptome remains elusive. Here, we systematically profile the chromatin accessibility, H3K4me3 and H3K27me3 modifications, and the transcriptome of intermediate progenitors during hematopoietic progenitor cell differentiation in vitro. The integrative analyses reveal sequential opening-up of regions for the binding of hematopoietic transcription factors and stepwise epigenetic reprogramming of bivalent genes. Single-cell analysis of cells undergoing the endothelial-to-hematopoietic transition and comparison with in vivo hemogenic endothelial cells reveal important features of in vitro and in vivo hematopoiesis. We find that JUNB is an essential regulator for hemogenic endothelium specialization and endothelial-to-hematopoietic transition. These studies depict an epigenomic roadmap from human pluripotent stem cells to hematopoietic progenitor cells, which may pave the way to generate hematopoietic progenitor cells with improved developmental potentials.

Date: 2022
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DOI: 10.1038/s41467-022-30789-4

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