Journal
DEVELOPMENTAL CELL
Volume 26, Issue 3, Pages 237-249Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2013.06.023
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Funding
- EuroSystem grant
- Leukaemia and Lymphoma Research programme grant
- MRC programme grant
- MRC [MC_U137973817, MC_U137981013, MC_UU_12009/8] Funding Source: UKRI
- Cancer Research UK [12796] Funding Source: researchfish
- Great Ormond Street Hospital Childrens Charity [W1062] Funding Source: researchfish
- Medical Research Council [G1000801a, MC_U137973817, MC_U137981013, MC_UU_12009/8] Funding Source: researchfish
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Hematopoietic stem cells (HSCs) emerge during embryogenesis from hemogenic endothelium, but it remains unclear how the HSC lineage is initially established from mesoderm during ontogeny. In Xenopus, the definitive hemangioblast precursors of the HSC lineage have been identified in dorsal lateral plate (DLP) mesoderm, and a transcriptional gene regulatory network (GRN) controlling hemangioblast programming has been elucidated. Herein, we identify an essential role for microRNAs (miRNAs) in establishing the mesodermal lineage leading to both HSC emergence and vasculogenesis and determine that a single miRNA, miR-142-3p, is primarily responsible for initiation of definitive hemangioblast specification. miR-142-3p forms a double-negative gate unlocking entry into the hemangioblast program, in part by inhibiting TGF beta signaling. Our results table miR-142-3p as a master regulator of HSC lineage specification, sitting at the apex of the hierarchy programming the adult hemangioblast, thus illustrating that miRNAs can act as instructive determinants of cell fate during development.
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