Journal
NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-28781-z
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Funding
- National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH) [RC2DK114777, R01DK110563]
- National Heart, Lung, And Blood Institute of the NIH [K08HL140143]
- American Society of Hematology Scholar Award
- Experimental Histopathology and Flow Cytometry Shared Resources of the Fred Hutch/University of Washington Cancer Consortium [P30 CA015704]
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In this study, the authors used single cell RNA-sequencing to map the signaling interactions regulating embryonic HSC development. They also engineered a niche that supports HSC maturation in vitro based on this knowledge.
Here, the authors use single cell RNA-sequencing to generate an atlas of signaling interactions regulating embryonic hematopoietic stem cell (HSC) development and apply this knowledge to engineer a niche sufficient to support HSC maturation in vitro. Hematopoietic stem cells (HSCs) develop from hemogenic endothelium within embryonic arterial vessels such as the aorta of the aorta-gonad-mesonephros region (AGM). To identify the signals responsible for HSC formation, here we use single cell RNA-sequencing to simultaneously analyze the transcriptional profiles of AGM-derived cells transitioning from hemogenic endothelium to HSCs, and AGM-derived endothelial cells which provide signals sufficient to support HSC maturation and self-renewal. Pseudotemporal ordering reveals dynamics of gene expression during the hemogenic endothelium to HSC transition, identifying surface receptors specifically expressed on developing HSCs. Transcriptional profiling of niche endothelial cells identifies corresponding ligands, including those signaling to Notch receptors, VLA-4 integrin, and CXCR4, which, when integrated in an engineered platform, are sufficient to support the generation of engrafting HSCs. These studies provide a transcriptional map of the signaling interactions necessary for the development of HSCs and advance the goal of engineering HSCs for therapeutic applications.
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