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

Autor: Richard A Axton, Michael Jackson, Maria Kydonaki, Tom Burdon, Stephen Meek, A. H. Taylor, Alexander Medvinsky, Antonella Fidanza, Stanislav Rybtsov, Lesley M. Forrester
Rok vydání: 2021
Předmět:
0301 basic medicine
Aplnr-tdTomato reporter ESCs
Peptide Hormones
Ligands
Biochemistry
APELIN
Mesoderm
Mice
0302 clinical medicine
Genes
Reporter
Induced pluripotent stem cell
Cells
Cultured
Cell Aggregation
Apelin Receptors
education.field_of_study
Chemistry
Hematopoietic Stem Cell Transplantation
Cell Differentiation
Mouse Embryonic Stem Cells
differentiation
Hedgehog signaling pathway
Apelin
Cell biology
Haematopoiesis
medicine.anatomical_structure
Stem cell
APLNR
Signal Transduction
Hemangioblasts
Population
Biology
Article
03 medical and health sciences
medicine
Genetics
Animals
Humans
Progenitor cell
education
Apelin receptor
Aplnr-null ESCs
AGM explant culture
Cell Biology
Hematopoietic Stem Cells
embryonic stem cell
Embryonic stem cell
hematopoiesis
Mice
Inbred C57BL
030104 developmental biology
Gene Expression Regulation
Gene Deletion
030217 neurology & neurosurgery
Developmental Biology
Zdroj: Stem Cell Reports
Jackson, M, Fidanza, A, Taylor, H, Rybtsov, S, Axton, R, Kydonaki, M, Meek, S, Burdon, T, Medvinsky, A & Forrester, L M 2021, ' Modulation of Aplnr signaling is required during the development and maintenance of the hematopoietic system ', Stem Cell Reports . https://doi.org/10.1016/j.stemcr.2021.02.003
ISSN: 2213-6711
Popis: Summary 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.
Graphical abstract
Highlights • Aplnr-tdTomato reporter marks a subpopulation of ESC-derived mesoderm • Hematopoietic differentiation is impaired in Aplnr-null ESCs • HSC activity within AGM explant cultures is reduced in the presence of Aplnr ligands • Aplnr signaling drives the maturation of lineage-committed myeloid progenitors
In this article, Lesley Forrester and colleagues use genetically engineered embryonic stem cells and explant cultures of embryonic aorta-mesonephros tissue to show that APLNR signaling is required for the generation of cells that give rise to hematopoietic cells but that its subsequent downregulation is required for the maintenance of hematopoietic stem cells.
Databáze: OpenAIRE
Externí odkaz: