Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-04893-3
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Funding
- European Research Council grant (ERC) [220-H75001EU/HSCOrigin-309361]
- NWO/ZonMw [912.15.017]
- UMC Utrecht Regenerative Medicine Stem Cells
- Medical Research Council [MR/P000673/1]
- Biotechnology and Biological Sciences Research Council [BB/I001794/1]
- Bloodwise [12037]
- European Union's Horizon 2020 [GA6586250]
- Cancer Research UK [C5759/A20971]
- TOP-subsidy NWO/CW [714.016.001]
- BBSRC [BB/I001794/1] Funding Source: UKRI
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Haematopoietic stem cells (HSCs) are generated from haemogenic endothelial (HE) cells via the formation of intra-aortic haematopoietic clusters (IAHCs) in vertebrate embryos. The molecular events controlling endothelial specification, endothelial-to-haematopoietic transition (EHT) and IAHC formation, as it occurs in vivo inside the aorta, are still poorly understood. To gain insight in these processes, we performed single-cell RNA-sequencing of non-HE cells, HE cells, cells undergoing EHT, IAHC cells, and whole IAHCs isolated from mouse embryo aortas. Our analysis identified the genes and transcription factor networks activated during the endothelial-to-haematopoietic switch and IAHC cell maturation toward an HSC fate. Our study provides an unprecedented complete resource to study in depth HSC generation in vivo. It will pave the way for improving HSC production in vitro to address the growing need for tailor-made HSCs to treat patients with blood-related disorders.
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