| First Author | Chandrakanthan V | Year | 2022 |
| Journal | Nat Cell Biol | Volume | 24 |
| Issue | 8 | Pages | 1211-1225 |
| PubMed ID | 35902769 | Mgi Jnum | J:332316 |
| Mgi Id | MGI:7414445 | Doi | 10.1038/s41556-022-00955-3 |
| Citation | Chandrakanthan V, et al. (2022) Mesoderm-derived PDGFRA(+) cells regulate the emergence of hematopoietic stem cells in the dorsal aorta. Nat Cell Biol 24(8):1211-1225 |
| abstractText | 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 (Mesp1(der) PSCs) 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 (Wnt1(der) PSCs). Co-aggregating non-haemogenic endothelial cells with Mesp1(der) PSCs but not Wnt1(der) PSCs 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-mesonephros Mesp1(der) PSCs could potentially be harnessed to manufacture LT-HSCs from endothelium. |
