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Smarca5-mediated epigenetic programming facilitates fetal HSPC development in vertebrates
- Source :
- Blood. 137:190-202
- Publication Year :
- 2021
- Publisher :
- American Society of Hematology, 2021.
-
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.
- Subjects :
- 0301 basic medicine
Immunology
Cell Biology
Hematology
Biology
biology.organism_classification
Biochemistry
Chromatin remodeling
Chromatin
Cell biology
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Epigenetics
Progenitor cell
Zebrafish
Transcription factor
Nucleolin
030217 neurology & neurosurgery
Epigenesis
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 137
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi...........3dd63a6cb6ac813bcd4f864409eb8220