title: MiR-142-3p controls the specification of definitive hemangioblasts during ontogeny.
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.
authors.affiliation: Stem Cell Laboratory, UCL Cancer Institute, WC1E 6BT London, UK. r.nimmo@ucl.ac.uk
authors.forename: Rachael
authors.initials: R
authors.lastname: Nimmo
authors.forename: Aldo
authors.initials: A
authors.lastname: Ciau-Uitz
authors.forename: Cristina
authors.initials: C
authors.lastname: Ruiz-Herguido
authors.forename: Shamit
authors.initials: S
authors.lastname: Soneji
authors.forename: Anna
authors.initials: A
authors.lastname: Bigas
authors.forename: Roger
authors.initials: R
authors.lastname: Patient
authors.forename: Tariq
authors.initials: T
authors.lastname: Enver
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage / Q000502:physiology; D047108:Embryonic Development / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D055018:Hemangioblasts / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D060172:Morpholinos; D018919:Neovascularization, Physiologic / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D016601:RNA-Binding Proteins; D014982:Xenopus laevis
chemical_list: C474044:Dgcr8 protein, mouse; C584035:MIRN142 microRNA, Xenopus; D035683:MicroRNAs; C529102:Mirn142 microRNA, mouse; D060172:Morpholinos; D011506:Proteins; D016601:RNA-Binding Proteins