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: |