Mesoderm-Derived PDGFRA + Cells Regulate the Emergence of Hematopoietic Stem Cells in the Dorsal Aorta
Mesoderm-Derived PDGFRA + Cells Regulate the Emergence of Hematopoietic Stem Cells in the Dorsal Aorta
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中胚层衍生的 PDGFRA 细胞调节背主动脉造血干细胞的出现
DOI：
10.1101/2021.08.08.455592
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Chandrakanthan V
中科院分区：
文献类型：
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作者：
Chandrakanthan V
小鼠造血干细胞（hsc）在胚胎第10.5天（E10.5）在背主动脉腹侧表面通过内皮细胞向造血细胞的过渡首次出现。我们研究了间充质干细胞是否存在于主动脉-性腺-中肾，并促进背主动脉的发育和内皮细胞向造血细胞的转变。间充质干细胞为骨髓中长期造血干细胞（lt - hsc）提供了必要的生态位。本研究表明，中胚层来源的PDGFRA+基质细胞（Mesp1derPSCs）促进了背主动脉的造血内皮，并填充了E10.5-E11.5主动脉-性腺-中肾，但E13.5被神经嵴来源的PSCs （Wnt1derPSCs）所取代。非造血内皮细胞与mesp1derpscs和notnt1derpscs共聚集导致内皮细胞中造血转录程序的激活和lt - hsc的生成。PDGFRA或BMP、WNT和NOTCH信号的剂量依赖性抑制中断了这一重编程事件。总之，主动脉-性腺-中肾smesp1derpscs有可能利用内皮细胞制造lt - hsc。
Mouse haematopoietic stem cells (HSCs) first emerge at embryonic day 10.5 (E10.5), on the ventral surface of the dorsal aorta, by endothelial-to-haematopoietic transition. We investigated whether mesenchymal stem cells, which provide an essential niche for long-term HSCs (LT-HSCs) in the bone marrow, reside in the aorta–gonad–mesonephros and contribute to the development of the dorsal aorta and endothelial-to-haematopoietic transition. Here we show that mesoderm-derived PDGFRA+stromal cells (Mesp1derPSCs) contribute to the haemogenic endothelium of the dorsal aorta and populate the E10.5–E11.5 aorta–gonad–mesonephros but by E13.5 were replaced by neural-crest-derived PSCs (Wnt1derPSCs). Co-aggregating non-haemogenic endothelial cells withMesp1derPSCs but notWnt1derPSCs resulted in activation of a haematopoietic transcriptional programme in endothelial cells and generation of LT-HSCs. Dose-dependent inhibition of PDGFRA or BMP, WNT and NOTCH signalling interrupted this reprogramming event. Together, aorta–gonad–mesonephrosMesp1derPSCs could potentially be harnessed to manufacture LT-HSCs from endothelium.