The TGFβ pathway is a key player for the endothelial-to-hematopoietic transition in the embryonic aorta

Dev Biol. 2018 Feb 15;434(2):292-303. doi: 10.1016/j.ydbio.2017.12.006. Epub 2017 Dec 16.

Abstract

The embryonic aorta produces hematopoietic stem and progenitor cells from a hemogenic endothelium localized in the aortic floor through an endothelial to hematopoietic transition. It has been long proposed that the Bone Morphogenetic Protein (BMP)/Transforming Growth Factor ß (TGFß) signaling pathway was implicated in aortic hematopoiesis but the very nature of the signal was unknown. Here, using thorough expression analysis of the BMP/TGFß signaling pathway members in the endothelial and hematopoietic compartments of the aorta at pre-hematopoietic and hematopoietic stages, we show that the TGFß pathway is preferentially balanced with a prominent role of Alk1/TgfßR2/Smad1 and 5 on both chicken and mouse species. Functional analysis using embryonic stem cells mutated for Acvrl1 revealed an enhanced propensity to produce hematopoietic cells. Collectively, we reveal that TGFß through the Alk1/TgfßR2 receptor axis is acting on endothelial cells to produce hematopoiesis.

Keywords: Alk1; Aorta; ES cells; Embryo; Endothelial-to-hematopoietic transition; Endothelium; Hematopoieisis; TGFß.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / cytology
  • Aorta / embryology*
  • Avian Proteins / metabolism*
  • Chick Embryo
  • Chickens
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / embryology*
  • Hematopoiesis, Extramedullary / physiology*
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / metabolism
  • Signal Transduction / physiology*
  • Smad1 Protein / metabolism
  • Smad5 Protein / metabolism
  • Transforming Growth Factor beta / metabolism*

Substances

  • Avian Proteins
  • Receptors, Transforming Growth Factor beta
  • Smad1 Protein
  • Smad5 Protein
  • Transforming Growth Factor beta
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II