title: The Etv2-miR-130a Network Regulates Mesodermal Specification.
abstract: MicroRNAs (miRNAs) are known to regulate critical developmental stages during embryogenesis. Here, we defined an Etv2-miR-130a cascade that regulates mesodermal specification and determination. Ablation of Dicer in the Etv2-expressing precursors resulted in altered mesodermal lineages and embryonic lethality. We identified miR-130a as a direct target of Etv2 and demonstrated its role in the segregation of bipotent hemato-endothelial progenitors toward the endothelial lineage. Gain-of-function experiments demonstrated that miR-130a promoted the endothelial program at the expense of the cardiac program without impacting the hematopoietic lineages. In contrast, CRISPR/Cas9-mediated knockout of miR-130a demonstrated a reduction of the endothelial program without affecting hematopoiesis. Mechanistically, miR-130a directly suppressed Pdgfra expression and promoted the endothelial program by blocking Pdgfra signaling. Inhibition or activation of Pdgfra signaling phenocopied the miR-130a overexpression and knockout phenotypes, respectively. In summary, we report the function of a miRNA that specifically promotes the divergence of the hemato-endothelial progenitor to the endothelial lineage.
authors.affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Bhairab N
authors.initials: BN
authors.lastname: Singh
authors.affiliation: Department of Genetics, Cell Biology and Development University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Department of Genetics, Cell Biology and Development University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Akiyama
authors.affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Rasmussen
authors.affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Mary G
authors.initials: MG
authors.lastname: Garry
authors.affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Wuming
authors.initials: W
authors.lastname: Gong
authors.affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Satyabrata
authors.initials: S
authors.lastname: Das
authors.affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Shi
authors.affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Naoko
authors.initials: N
authors.lastname: Koyano-Nakagawa
authors.affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: garry@umn.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Garry
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000378:metabolism; D006410:Hematopoiesis; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C503994:ER71 protein, mouse; C582652:MIRN130 microRNA, mouse; D035683:MicroRNAs; D014157:Transcription Factors; D020796:Receptor, Platelet-Derived Growth Factor alpha
keywords: Etv2; dicer; lineage specification; miR-130a; microRNA