TY - JOUR
T1 - Single-cell transcriptomics reveal the dynamic of haematopoietic stem cell production in the aorta
AU - Baron, Chloé S.
AU - Kester, Lennart
AU - Klaus, Anna
AU - Boisset, Jean Charles
AU - Thambyrajah, Roshana
AU - Yvernogeau, Laurent
AU - Kouskoff, Valérie
AU - Lacaud, Georges
AU - Van Oudenaarden, Alexander
AU - Robin, Catherine
N1 - Funding Information:
The authors thank the lab members for helpful discussion and various technical help. We would like to thank Jens Eberhardt and Michael Hollstein for their help to develop the automated cell picking of wIAHCs with the CellCellectorTM. We also thank the Animal Facility for mouse care and the Optical Imaging Center for confocal microscope access (both at the Hubrecht Institute). We thank Reinier van der Linden (Hubrecht Institute), and Jeroen van Velzen and Pien van der Burght (UMC Utrecht) for help with cell sorting. This work was supported in CR lab by a European Research Council grant (ERC, project number 220-H75001EU/HSCOrigin-309361), a TOP8861-subsidy from NWO/ZonMw (912.15.017), and the UMC Utrecht “Regenerative Medicine & Stem Cells” priority research program, in G.L. and V.K. labs by the Medical Research Council (MR/P000673/1), the Biotechnology and Biological Sciences Research Council (BB/I001794/1), Bloodwise (12037), the European Union’s Horizon 2020 (GA6586250) and Cancer Research UK (C5759/A20971), and in A. v O. lab by a TOP-subsidy NWO/ CW (714.016.001).
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/6/28
Y1 - 2018/6/28
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85049233523
U2 - 10.1038/s41467-018-04893-3
DO - 10.1038/s41467-018-04893-3
M3 - Article
C2 - 29955049
AN - SCOPUS:85049233523
SN - 2041-1723
VL - 9
SP - 1
EP - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2517
ER -