Yanyan Ding: State Key Laboratory of Membrane Biology, Institute of Zoology.
Wen Wang: Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Science and Technology, Shanghai Key Laboratory of Signaling and Disease Research, Tongji University, Shanghai, China; and.
Dongyuan Ma: State Key Laboratory of Membrane Biology, Institute of Zoology.
Guixian Liang: State Key Laboratory of Membrane Biology, Institute of Zoology.
Zhixin Kang: State Key Laboratory of Membrane Biology, Institute of Zoology.
Yuanyuan Xue: State Key Laboratory of Membrane Biology, Institute of Zoology.
Yifan Zhang: State Key Laboratory of Membrane Biology, Institute of Zoology.
Lu Wang: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences-Peking Union Medical College, Tianjin, China.
Jian Heng: State Key Laboratory of Membrane Biology, Institute of Zoology.
Yong Zhang: Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Science and Technology, Shanghai Key Laboratory of Signaling and Disease Research, Tongji University, Shanghai, China; and.
Feng Liu: State Key Laboratory of Membrane Biology, Institute of Zoology.
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.
