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

doi:10.1016/j.stemcr.2021.02.003

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 journal › Article › peer-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 language	English
Journal	Stem Cell Reports
Early online date	23 Feb 2021
DOIs	https://doi.org/10.1016/j.stemcr.2021.02.003
Publication status	Published - 4 Mar 2021

Keywords

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

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10.1016/j.stemcr.2021.02.003

PIIS2213671121000837Final published version, 3.01 MBLicence: Creative Commons: Attribution (CC-BY)

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@article{2bc9d919ebd244ff95f09105a39877f1,

title = "Modulation of Aplnr signaling is required during the development and maintenance of the hematopoietic system",

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",

keywords = "APLNR, embryonic stem cell, differentiation, hematopoiesis, APELIN, Aplnr-tdTomato reporter ESCs, Aplnr-null ESCs",

author = "Melany Jackson and Antonella Fidanza and Helen Taylor and Stanislav Rybtsov and Richard Axton and Maria Kydonaki and Stephen Meek and Tom Burdon and Alexander Medvinsky and Forrester, {Lesley M}",

year = "2021",

month = mar,

day = "4",

doi = "10.1016/j.stemcr.2021.02.003",

language = "English",

journal = "Stem Cell Reports",

issn = "2213-6711",

publisher = "Cell Press",

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Modulation of Aplnr signaling is required during the development and maintenance of the hematopoietic system. / Jackson, Melany; Fidanza, Antonella ; Taylor, Helen ; Rybtsov, Stanislav; Axton, Richard; Kydonaki, Maria; Meek, Stephen ; Burdon, Tom ; Medvinsky, Alexander ; Forrester, Lesley M.

In: Stem Cell Reports, 04.03.2021.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Modulation of Aplnr signaling is required during the development and maintenance of the hematopoietic system

AU - Jackson, Melany

AU - Fidanza, Antonella

AU - Taylor, Helen

AU - Rybtsov, Stanislav

AU - Axton, Richard

AU - Kydonaki, Maria

AU - Meek, Stephen

AU - Burdon, Tom

AU - Medvinsky, Alexander

AU - Forrester, Lesley M

PY - 2021/3/4

Y1 - 2021/3/4

N2 - 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

AB - 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

KW - APLNR

KW - embryonic stem cell

KW - differentiation

KW - hematopoiesis

KW - APELIN

KW - Aplnr-tdTomato reporter ESCs

KW - Aplnr-null ESCs

U2 - 10.1016/j.stemcr.2021.02.003

DO - 10.1016/j.stemcr.2021.02.003

M3 - Article

JO - Stem Cell Reports

JF - Stem Cell Reports

SN - 2213-6711

ER -