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Developmental cell
07 24, 2023;58 (14): 1237-1249.e5.

MicroRNA-223 limits murine hemogenic endothelial cell specification and myelopoiesis.

Yinyu Wu, Umadevi Paila, Gael Genet, Karen K Hirschi
Author Information
  1. Yinyu Wu: Departments of Genetics, Yale Cardiovascular Research Center, Vascular Biology and Therapeutics Program, Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Cell Biology, Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA.
  2. Umadevi Paila: Department of Cell Biology, Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA.
  3. Gael Genet: Department of Cell Biology, Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA.
  4. Karen K Hirschi: Departments of Genetics, Yale Cardiovascular Research Center, Vascular Biology and Therapeutics Program, Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Cell Biology, Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA. Electronic address: kkh4yy@virginia.edu.
PMID: 37295435 DOI: 10.1016/j.devcel.2023.05.007

Abstract

Embryonic definitive hematopoiesis generates hematopoietic stem and progenitor cells (HSPCs) that are essential for the establishment and maintenance of the adult blood system. This process requires the specification of a subset of vascular endothelial cells (ECs) to become hemogenic ECs and to have subsequent endothelial-to-hematopoietic transition (EHT), and the underlying mechanisms are largely undefined. We identified microRNA (miR)-223 as a negative regulator of murine hemogenic EC specification and EHT. Loss of miR-223 leads to increased formation of hemogenic ECs and HSPCs, which is associated with increased retinoic acid signaling, which we previously showed as promoting hemogenic EC specification. Additionally, loss of miR-223 leads to the generation of myeloid-biased hemogenic ECs and HSPCs, which results in an increased proportion of myeloid cells throughout embryonic and postnatal life. Our findings identify a negative regulator of hemogenic EC specification and highlight the importance of this process for the establishment of the adult blood system.

Keywords

MicroRNA-223 hematopoiesis hematopoietic stem cells hemogenic endothelial cells myelopoiesis retinoic acid signaling

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Grants

  1. R01 DK118728/NIDDK NIH HHS
  2. R01 HL146056/NHLBI NIH HHS
  3. UH2 EB017103/NIBIB NIH HHS

MeSH Term

Mice
Animals
Hemangioblasts
Myelopoiesis
Hematopoietic Stem Cells
Hematopoiesis
Cell Differentiation
MicroRNAs

Chemicals

MicroRNAs
MIRN223 microRNA, mouse
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Article has an altmetric score of 10

Word Cloud

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