Modulation of APLNR Signaling Is Required during the Development and Maintenance of the Hematopoietic System.
Modulation of APLNR Signaling Is Required during the Development and Maintenance of the Hematopoietic System.
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DOI：
10.1016/j.stemcr.2021.02.003
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发表时间：
2021-04-13
影响因子：
5.9
通讯作者：
Forrester LM
中科院分区：
文献类型：
--
作者：
Jackson M;Fidanza A;Taylor AH;Rybtsov S;Axton R;Kydonaki M;Meek S;Burdon T;Medvinsky A;Forrester LM
爱帕琳受体（Apelin receptor，APLNR/AGTRL 11/APJ）是多能干细胞向造血干细胞和祖细胞（hematopoietic stem and progenitor cells，HSPCs）分化过程中的一个瞬时细胞群，但其在造血干细胞生成和维持过程中的作用尚不清楚。我们产生了Aplnr-tdTomato报告基因小鼠胚胎干细胞（mESC）系，并表明HSPC仅由表达Aplnr-tdTomato的中胚层细胞产生。当Aplnr缺失时，来自mESC的HSPC生产受损，这意味着该途径是其生产所必需的。为了解决APLNR信号传导在HSPC维持中的作用，我们将APELIN配体添加到离体AGM培养物中。该系统中APLNR通路的激活损害了长期重建HSPC的产生，并似乎驱动了骨髓分化。我们的数据表明，APLNR信号传导是产生HSC的细胞产生所必需的，但其随后的下调是维持HSC所必需的。Aplnr-tdTomato报告基因标记ESC衍生的中胚层亚群造血分化在Aplnr缺失的ESC中受损AGM外植体培养物内的HSC活性在Aplnr配体存在下降低Aplnr信号传导驱动谱系定向髓样祖细胞的成熟在这篇文章中，莱斯利·福雷斯特和他的同事们使用基因工程胚胎干细胞和胚胎主动脉的外植体培养物，中肾组织的研究表明，APLNR信号传导是产生造血细胞的细胞所需的，但其随后的下调是维持造血干细胞所需的。
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. 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.
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影响因子：
3.7
作者：
Axton RA;Haideri SS;Lopez-Yrigoyen M;Taylor HA;Forrester LM
通讯作者：
Forrester LM
影响因子：
6
作者：
Jackson M;Ma R;Taylor AH;Axton RA;Easterbrook J;Kydonaki M;Olivier E;Marenah L;Stanley EG;Elefanty AG;Mountford JC;Forrester LM
通讯作者：
Forrester LM
影响因子：
8.8
作者：
McGrath KE;Frame JM;Fegan KH;Bowen JR;Conway SJ;Catherman SC;Kingsley PD;Koniski AD;Palis J
通讯作者：
Palis J
影响因子：
7.7
作者：
Malaguti M;Nistor PA;Blin G;Pegg A;Zhou X;Lowell S
通讯作者：
Lowell S
影响因子：
5.9
作者：
Batsivari A;Rybtsov S;Souilhol C;Binagui-Casas A;Hills D;Zhao S;Travers P;Medvinsky A
通讯作者：
Medvinsky A