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Updated: Apr 27, 2026

Development of an In Vitro Assay to Quantitate Hematopoietic Stem and Progenitor Cells HSPCs in Developing Zebrafish Embryos
Published on: November 30, 2017
Ncor2 is required for hematopoietic stem cell emergence by inhibiting Fos signaling in zebrafish
Yonglong Wei1, Dongyuan Ma1, Ya Gao1
1State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Abstract:
Nuclear receptor corepressors (Ncors) are important for developmental and homeostatic processes in vertebrates, which exert transcriptional repression by coordinating with histone deacetylases. However, little is known about their roles in definitive hematopoiesis. In this study, we show that in zebrafish, ncor2 is required for hematopoietic stem cell (HSC) development by repressing fos-vegfd signaling. ncor2 is specifically expressed in the aorta-gonad-mesonephros (AGM) region in zebrafish embryos. ncor2 deficiency reduced the population of HSCs in both the AGM region and T cells in the thymus. Mechanistically, ncor2 knockdown upregulated fos transcription by modulating the acetylation level in the fos promoter region, which then enhanced Vegfd signaling. Consequently, the augmented Vegfd signaling induced Notch signaling to promote the arterial endothelial fate, therefore, possibly repressing the hemogenic endothelial specification, which is a prerequisite for HSC emergence. Thus, our findings identify a novel regulatory mechanism for Ncor2 through Fos-Vegfd-Notch signaling cascade during HSC development in zebrafish embryos.
Insights
Nuclear receptor corepressor 2 (ncor2) is crucial for zebrafish hematopoietic stem cell (HSC) development. It represses fos-vegfd signaling, ensuring proper HSC emergence during embryonic development.
Area of Science:
- Developmental Biology
- Hematopoiesis
- Molecular Biology
Background:
- Nuclear receptor corepressors (Ncors) regulate vertebrate development and homeostasis.
- The function of Ncors in definitive hematopoiesis remains largely unexplored.
Purpose of the Study:
- To investigate the role of ncor2 in hematopoietic stem cell (HSC) development in zebrafish embryos.
- To elucidate the molecular mechanisms by which ncor2 influences HSC emergence.
Main Methods:
- Zebrafish embryo studies to examine ncor2 expression patterns.
- Analysis of HSC populations in ncor2-deficient zebrafish.
- Investigation of gene transcription and signaling pathways (fos, Vegfd, Notch) in ncor2 knockdown embryos.
Main Results:
- ncor2 is specifically expressed in the aorta-gonad-mesonephros (AGM) region of zebrafish embryos.
- ncor2 deficiency leads to reduced HSCs in the AGM region and decreased T cells in the thymus.
- ncor2 knockdown upregulates fos transcription, enhances Vegfd signaling, and promotes arterial endothelial fate via Notch signaling, potentially inhibiting hemogenic endothelial specification.
Conclusions:
- ncor2 plays a critical role in HSC development in zebrafish.
- ncor2 acts by repressing the Fos-Vegfd-Notch signaling cascade, which is essential for HSC emergence.
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