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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造血系统的发育和维持过程中需要调节 Aplnr 信号
DOI：
10.1101/2020.06.15.145649
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Jackson M
中科院分区：
文献类型：
--
作者：
Jackson M
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。我们建立了一个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，我们向离体AGM培养物中加入APELIN配体。该系统中APLNR途径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。
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 anAplnr-tdTomato reporter mouse embryonic stem cell (mESC) line and showed that HSPCs are generated exclusively from mesodermal cells that expressAplnr-tdTomato. HSPC production from mESCs was impaired whenAplnrwas deleted, implying that this pathway is required for their production. To address the role of APLNR signaling in HSPC maintenance, we added APELIN ligands toex vivoAGM 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.