Hematopoietic stem and progenitor cells (HSPCs) are multipotent cells that self-renew or differentiate to establish the entire blood hierarchy. HSPCs arise from the hemogenic endothelium of the dorsal aorta (DA) during development in a process called endothelial-to-hematopoietic transition. The factors and signals that control HSPC fate decisions from the hemogenic endothelium are not fully understood. We found that vegfc has a role in HSPC emergence from the zebrafish DA. Using time-lapse live imaging, we show that some HSPCs in the DA of vegfc loss-of-function embryos display altered cellular behavior. Instead of typical budding from the DA, emergent HSPCs exhibit crawling behavior similar to myeloid cells. This was confirmed by increased myeloid cell marker expression in the ventral wall of the DA and the caudal hematopoietic tissue. This increase in myeloid cells corresponded with a decrease in HSPCs that persisted into larval stages. Together, our data suggests vegfc regulates HSPC emergence in the hemogenic endothelium, in part by suppressing a myeloid cell fate. Our study provides a potential signal for modulation of HSPC fate in stem cell differentiation protocols.
Vascular endothelial growth factor-c regulates hematopoietic stem cell fate in the dorsal aorta
Present address: Department of Cell and Regenerative Biology, University of Wisconsin – Madison, Madison WI 53705 USA
- Award Group:
- Funder(s): National Institutes of Health
- Award Id(s): R01HL142998
- Funder(s):
- Award Group:
- Funder(s): American Society of Hematology
- Award Id(s): ASH Scholar Award
- Funder(s):
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Rebecca K. Schiavo, Owen J. Tamplin; Vascular endothelial growth factor-c regulates hematopoietic stem cell fate in the dorsal aorta. Development 2021; dev.199498. doi: https://doi.org/10.1242/dev.199498
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