Single-cell transcriptomics reveal the dynamic of haematopoietic stem cell production in the aorta

• Published in: Nature communications Vol. 9; no. 1; pp. 2517 - 15
• Main Authors: Baron, Chloé S., Kester, Lennart, Klaus, Anna, Boisset, Jean-Charles, Thambyrajah, Roshana, Yvernogeau, Laurent, Kouskoff, Valérie, Lacaud, Georges, van Oudenaarden, Alexander, Robin, Catherine
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28-06-2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 14/19; 45; 45/100; 45/91; 631/136/532/1542; 631/80/86; 64/60; 82/1; Animals; Aorta; Aorta - cytology; Aorta - growth & development; Aorta - metabolism; Cell Differentiation; Cell Lineage; Coronary vessels; Embryo, Mammalian; Embryos; Female; Gene Expression Regulation, Developmental; Gene Ontology; Gene Regulatory Networks; Gene sequencing; Hemangioblasts - cytology; Hemangioblasts - metabolism; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Humanities and Social Sciences; In vivo methods and tests; Mice; Mice, Inbred C57BL; Molecular chains; Molecular Sequence Annotation; multidisciplinary; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Single-Cell Analysis; Stem cell transplantation; Stem cells; Switching theory; Transcriptome
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-04893-3

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.
Haematopoietic stem cells (HSCs) are generated from haemogenic endothelial (HE) cells in vertebrate embryo aortas. Here, the authors perform single-cell RNA-sequencing of cells isolated from embryonic mouse aortas to identify genes and transcription factor networks activated during the endothelial-to-haematopoietic switch.