Mesoderm-derived PDGFRA + cells regulate the emergence of hematopoietic stem cells in the dorsal aorta.
Vashe ChandrakanthanPrunella RorimpandeyFabio ZaniniDiego ChaconJake OlivierSwapna JoshiYoung Chan KangKathy KnezevicYizhou HuangQiao QiaoRema A OliverAshwin UnnikrishnanDaniel R CarterBrendan LeeChris BrownleeCarl PowerRobert BrinkSimon Mendez-FerrerGrigori EnikolopovWilliam WalshBerthold GöttgensSamir TaoudiDominik BeckJohn E PimandaPublished in: Nature cell biology (2022)
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.
Keyphrases
- stem cells
- aortic valve
- endothelial cells
- pulmonary artery
- mesenchymal stem cells
- spinal cord
- bone marrow
- neuropathic pain
- cell proliferation
- coronary artery
- nitric oxide
- pulmonary hypertension
- aortic dissection
- gene expression
- cell therapy
- umbilical cord
- spinal cord injury
- high glucose
- high resolution
- vascular endothelial growth factor
- mass spectrometry