| Literature DB >> 32756943 |
Yanyan Ding1,2,3, Wen Wang4, Dongyuan Ma1,2,3, Guixian Liang1,2,3, Zhixin Kang1,2,3, Yuanyuan Xue1,2,3, Yifan Zhang1,2,3, Lu Wang5, Jian Heng1,2,3, Yong Zhang4, Feng Liu1,2,3.
Abstract
Nascent hematopoietic stem and progenitor cells (HSPCs) acquire definitive hematopoietic characteristics only when they develop into fetal HSPCs; however, the mechanisms underlying fetal HSPC development are poorly understood. Here, we profiled the chromatin accessibility and transcriptional features of zebrafish nascent and fetal HSPCs using ATAC-seq and RNA-seq and revealed dynamic changes during HSPC transition. Functional assays demonstrated that chromatin remodeler-mediated epigenetic programming facilitates fetal HSPC development in vertebrates. Systematical screening of chromatin remodeler-related genes identified that smarca5 is responsible for the maintenance of chromatin accessibility at promoters of hematopoiesis-related genes in fetal HSPCs. Mechanistically, Smarca5 interacts with nucleolin to promote chromatin remodeling, thereby facilitating genomic binding of transcription factors to regulate expression of hematopoietic regulators such as bcl11ab. Our results unravel a new role of epigenetic regulation and reveal that Smarca5-mediated epigenetic programming is responsible for fetal HSPC development, which will provide new insights into the generation of functional HSPCs both in vivo and in vitro.Entities:
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Year: 2021 PMID： 32756943 PMCID： PMC7820875 DOI： 10.1182/blood.2020005219
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113