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Dev Cell 2013 Aug 12;263:237-49. doi: 10.1016/j.devcel.2013.06.023.
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MiR-142-3p controls the specification of definitive hemangioblasts during ontogeny.

Nimmo R , Ciau-Uitz A , Ruiz-Herguido C , Soneji S , Bigas A , Patient R , Enver T .

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 TGFβ 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.

PubMed ID: 23911199
Article link: Dev Cell
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: acvr1b acvr2a cd93 dct dgcr8 dll4 etv2 fli1 flt1 flt4 gata2 gfi1 gja4 grn kdr kit pecam1 psma7 ptprc runx1 spib tal1 tbx2 tgfb1 tgfbr1
Morpholinos: dgcr8 MO1 miR-142-3p MO miR-142-5p MO

Article Images: [+] show captions