Journal
DEVELOPMENT
Volume 140, Issue 19, Pages 3977-3985Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.097071
Keywords
Zebrafish; Scl; Tal1; Hemogenic endothelium; Hematopoietic stem cells
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Funding
- National Basic Research Program of China [2012CB945102]
- National Natural Science Foundation of China [31171403, 30828020]
- General Research Fund (GRF)
- Research Grants Council of the Hong Kong Special Administrative Region [HKUST6/CRF/09, 663111, 663212]
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Recent studies have shown that nascent hematopoietic stem cells (HSCs) derive directly from the ventral aortic endothelium (VAE) via endothelial to hematopoietic transition (EHT). However, whether EHT initiates from a random or predetermined subpopulation of VAE, as well as the molecular mechanism underlying this process, remain unclear. We previously reported that different zebrafish stem cell leukemia (scl) isoforms are differentially required for HSC formation in the ventral wall of the dorsal aorta. However, the exact stage at which these isoforms impact HSC development was not defined. Here, using in vivo time-lapse imaging of scl isoformspecific reporter transgenic zebrafish lines, we show that prior to EHT scl-beta is selectively expressed in hemogenic endothelial cells, a unique subset of VAE cells possessing hemogenic potential, whereas scl-alpha is expressed later in nascent HSCs as they egress from VAE cells. In accordance with their expression, loss-of-function studies coupled with in vivo imaging analysis reveal that scl-beta acts earlier to specify hemogenic endothelium, which is later transformed by runx1 into HSCs. Our results also reveal a previously unexpected role of scl-alpha in maintaining newly born HSCs in the aorta-gonads-mesonephros. Thus, our data suggest that a defined hemogenic endothelial population preset by scl-beta supports the deterministic emergence of HSCs, and unravel the cellular mechanisms by which scl isoforms regulate HSC development.
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