Mesoderm-Derived PDGFRA+Cells Regulate the Emergence of Hematopoietic Stem Cells in the Dorsal Aorta

crossref(2021)

引用 0|浏览3
暂无评分
摘要
AbstractMouse hematopoietic stem cells (HSCs) first emerge at embryonic day 10.5 (E10.5) on the ventral surface of the dorsal aorta, by endothelial-to-hematopoietic transition (EHT). We investigated whether cells with mesenchymal stem cell-like activity, which provide an essential niche for long-term HSCs (LT-HSCs) in the bone marrow, reside in the aorta- gonad-mesonephros (AGM) and contribute to the structural development of the dorsal aorta and EHT. Using transgenic mice, we demonstrate a lineage hierarchy for AGM stromal cells and traced the E10.5/E11.5 aortic endothelium and HSCs to mesoderm derived (Mesp1) PDGFRA+stromal cells (Mesp1derPSCs).Mesp1derPSCs dominate the sub-endothelial and ventral stroma in the E10.5–E11.5 AGM but by E13.5 were replaced by neural crest (Wnt1) derived PDGFRA+stromal cells (Wnt1derPSCs). Co-aggregating non-hemogenic embryonic and adult endothelial cells withMesp1derPSCs but not withWnt1derPSCs resulted in activation of a hematopoietic transcriptional program in endothelial cells accompanied by EHT and generation of LT-HSCs. Dose-dependent inhibition of PDGFRA signalling or BMP, WNT, NOTCH signalling interrupted this reprogramming event. This partnership between endothelial cells and AGMMesp1derPSCs could potentially be harnessed to manufacture LT-HSCs from endothelium.
更多
查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要