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Updated: Dec 12, 2025
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Reprogramming Mouse Embryonic Fibroblasts with Transcription Factors to Induce a Hemogenic Program
Published on: December 16, 2016
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Smarca5-mediated epigenetic programming facilitates fetal HSPC development in vertebrates
Yanyan Ding1,2,3, Wen Wang4, Dongyuan Ma1,2,3
1State Key Laboratory of Membrane Biology, Institute of Zoology.
Blood
|August 7, 2020
Summary
Epigenetic programming by the chromatin remodeler smarca5 is crucial for developing functional fetal hematopoietic stem and progenitor cells (HSPCs). This mechanism ensures proper gene regulation for definitive hematopoiesis.
Area of Science:
- Developmental Biology
- Epigenetics
- Hematopoiesis
Background:
- Nascent hematopoietic stem and progenitor cells (HSPCs) must mature into fetal HSPCs to gain definitive hematopoietic characteristics.
- The molecular mechanisms driving this critical developmental transition remain largely unknown.
Purpose of the Study:
- To elucidate the epigenetic mechanisms governing the transition from nascent to fetal HSPCs.
- To identify key regulators involved in fetal HSPC development.
Main Methods:
- Chromatin accessibility (ATAC-seq) and transcriptional profiling (RNA-seq) of zebrafish nascent and fetal HSPCs.
- Functional assays to assess the role of chromatin remodelers.
- Systematic screening of chromatin remodeler-related genes.
Main Results:
- Dynamic changes in chromatin accessibility and gene expression occur during HSPC development.
- Chromatin remodeler-mediated epigenetic programming is essential for fetal HSPC maturation.
- Smarca5 was identified as a key regulator maintaining chromatin accessibility at hematopoietic gene promoters in fetal HSPCs.
- Smarca5 interacts with nucleolin to facilitate transcription factor binding and regulate key hematopoietic genes like bcl11ab.
Conclusions:
- Smarca5 plays a critical role in fetal HSPC development through epigenetic programming.
- This study reveals a novel mechanism for generating functional HSPCs, offering insights for in vivo and in vitro applications.
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