Modulation of Aplnr signaling is required during the development and maintenance of the hematopoietic system

Melany Jackson, Antonella Fidanza, Helen Taylor, Stanislav Rybtsov, Richard Axton, Maria Kydonaki, Stephen Meek, Tom Burdon, Alexander Medvinsky, Lesley M Forrester

Research output: Contribution to journalArticlepeer-review

Abstract

Apelin receptor (Aplnr/Agtrl1/Apj) marks a transient cell population during the differentiation of hematopoietic stem and progenitor cells (HSPCs) from pluripotent stem cells but its function during the production and maintenance of haematopoietic stem cells is not clear. We generated an Aplnr-tdTomato reporter mouse embryonic stem cell (mESC) line and showed that HSPCs are generated exclusively from mesodermal cells that express Aplnr. HSPCs production from mESCs was impaired when Aplnr was deleted implying that this pathway is required for their production. To address the role of the Aplnr pathway in HSPC maintenance, we added Apelin ligands to ex vivo AGM cultures. Activation of the Aplnr pathway in this system impaired the generation of long-term reconstituting HSPCs and appeared to drive myeloid differentiation. Our data suggest that the Aplnr signalling is required for the generation of cells that give rise to HSCs but its subsequent down regulation is required for their maintenance
Original languageEnglish
JournalStem Cell Reports
Early online date23 Feb 2021
DOIs
Publication statusPublished - 4 Mar 2021

Keywords

  • APLNR
  • embryonic stem cell
  • differentiation
  • hematopoiesis
  • APELIN
  • Aplnr-tdTomato reporter ESCs
  • Aplnr-null ESCs

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