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XB-ART-48008
Dev Cell. August 12, 2013; 26 (3): 237-49.

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 .


Abstract
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: Medical Research Council , R01 DC005827-08 NIDCD NIH HHS , 12796 Cancer Research UK, MC_U137973817 Medical Research Council , MC_U137981013 Medical Research Council , MC_UU_12009/8 Medical Research Council , MC_U137973817 Medical Research Council , MC_U137981013 Medical Research Council , MC_UU_12009/8 Medical Research CouncilMedical Research Council , MRC_MC_U137973817 Medical Research Council , MRC_MC_U137981013 Medical Research Council , MRC_MC_UU_12009/8 Medical Research CouncilMedical Research Council , MC_U137973817 Medical Research Council , MC_U137981013 Medical Research Council , MC_UU_12009/8 Medical Research CouncilMedical Research Council

Genes referenced: acvr1b acvr2a cd93 dct dgcr8 dll4 etv2 fli1 flt1 flt3 flt4 gata2 gfi1 gja4 grn hba1 kdr kit pecam1 psma7 ptprc runx1 spib tal1 tbx2 tgfb1 tgfbr1

Morpholinos referenced: dgcr8 MO1 miR-142-3p MO miR-142-5p MO


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