Format

Send to

Choose Destination
See comment in PubMed Commons below
Dev Cell. 2013 Aug 12;26(3):237-49. doi: 10.1016/j.devcel.2013.06.023. Epub 2013 Aug 1.

MiR-142-3p controls the specification of definitive hemangioblasts during ontogeny.

Author information

1
Stem Cell Laboratory, UCL Cancer Institute, WC1E 6BT London, UK. r.nimmo@ucl.ac.uk

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.

PMID:
23911199
DOI:
10.1016/j.devcel.2013.06.023
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center