Reprogramming of 3D genome structure underlying HSPC development in zebrafish

作者全名：He, Min; Li, Xiaoli; Xu, Bingxiang; Lu, Yinbo; Lai, Jingyi; Ling, Yiming; Liu, Huakai; An, Ziyang; Zhang, Wenqing; Li, Feifei

作者地址：[He, Min; Li, Xiaoli; Lu, Yinbo; Lai, Jingyi; Ling, Yiming; Zhang, Wenqing; Li, Feifei] South China Univ Technol, Sch Med, Div Cell Dev & Integrat Biol, Guangzhou 510006, Peoples R China; [Li, Xiaoli] Chongqing Med Univ, Sch Basic Med Sci, Dept Cell Biol & Genet, Lab Dev Biol, Chongqing 400016, Peoples R China; [Xu, Bingxiang] Hebei Univ Technol, Inst Biophys, Sch Hlth Sci & Biomed Engn, Key Lab Hebei Prov Mol Biophys, Tianjin 300130, Peoples R China; [Liu, Huakai] South China Univ Technol, Sch Mech & Automot Engn, Vehicle Engn, Guangzhou 510000, Peoples R China; [An, Ziyang] Sun Yat Sen Univ, Sch Life Sci, State Key Lab Biocontrol, Guangzhou 510275, Peoples R China

通信作者：Zhang, WQ; Li, FF (通讯作者)，South China Univ Technol, Sch Med, Div Cell Dev & Integrat Biol, Guangzhou 510006, Peoples R China.

来源：STEM CELL RESEARCH & THERAPY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001249733000010

JCR分区：Q1

影响因子：7.1

年份：2024

卷号：15

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：HSPC; Chromatin conformation; Transcriptional regulation; Multi-omics dissection; PU.1

摘要：Background Development of hematopoietic stem and progenitor cells (HSPC) is a multi-staged complex process that conserved between zebrafish and mammals. Understanding the mechanism underlying HSPC development is a holy grail of hematopoietic biology, which is helpful for HSPC clinical application. Chromatin conformation plays important roles in transcriptional regulation and cell fate decision; however, its dynamic and role in HSPC development is poorly investigated.Methods We performed chromatin structure and multi-omics dissection across different stages of HSPC developmental trajectory in zebrafish for the first time, including Hi-C, RNA-seq, ATAC-seq, H3K4me3 and H3K27ac ChIP-seq.Results The chromatin organization of zebrafish HSPC resemble mammalian cells with similar hierarchical structure. We revealed the multi-scale reorganization of chromatin structure and its influence on transcriptional regulation and transition of cell fate during HSPC development. Nascent HSPC is featured by loose conformation with obscure structure at all layers. Notably, PU.1 was identified as a potential factor mediating formation of promoter-involved loops and regulating gene expression of HSPC.Conclusions Our results provided a global view of chromatin structure dynamics associated with development of zebrafish HSPC and discovered key transcription factors involved in HSPC chromatin interactions, which will provide new insights into the epigenetic regulatory mechanisms underlying vertebrate HSPC fate decision.

基金机构：Guangdong Natural Science Foundation [2023A1515030068]; National Nature Science Foundation of China [82270121]

基金资助正文：This work was supported by the Guangdong Natural Science Foundation (2023A1515030068, to Feifei Li), and the National Nature Science Foundation of China (grant no. 82270121, to Wenqing Zhang).