Modulation of APLNR Signaling Is Required During the Development and Maintenance of the Hematopoietic System

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2021 Mar 5

PMID 33667414

Citations 3

Authors

Melany Jackson

Antonella Fidanza

A Helen Taylor

Stanislav Rybtsov

Richard Axton

Maria Kydonaki

Stephen Meek

Tom Burdon

Alexander Medvinsky

Lesley M Forrester

Affiliations

Soon will be listed here.

Abstract

Apelin receptor (APLNR/AGTRLl1/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 hematopoietic 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-tdTomato. HSPC production from mESCs was impaired when Aplnr was deleted, implying that this pathway is required for their production. To address the role of APLNR signaling 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 signaling is required for the generation of cells that give rise to HSCs, but that its subsequent downregulation is required for their maintenance.

Citing Articles

Step by step analysis on gene datasets of growth phases in hematopoietic stem cells.

Elahimanesh M, Shokri N, Mohammadi P, Parvaz N, Najafi M Biochem Biophys Rep. 2024; 39:101737.

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Clonal and Scalable Endothelial Progenitor Cell Lines from Human Pluripotent Stem Cells.

Lee J, Sternberg H, Bignone P, Murai J, Malik N, West M Biomedicines. 2023; 11(10).

PMID: 37893151 PMC: 10604251. DOI: 10.3390/biomedicines11102777.

Progress in the production of haematopoietic stem and progenitor cells from human pluripotent stem cells.

Fidanza A, Forrester L J Immunol Regen Med. 2021; 13:100050.

PMID: 34405125 PMC: 8350141. DOI: 10.1016/j.regen.2021.100050.

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