Journal article

Human definitive haemogenic endothelium and arterial vascular endothelium represent distinct lineages

Andrea Ditadi, Christopher M Sturgeon, Joanna Tober, Geneve Awong, Marion Kennedy, Amanda D Yzaguirre, Lisa Azzola, Elizabeth S Ng, Edouard G Stanley, Deborah L French, Xin Cheng, Paul Gadue, Nancy A Speck, Andrew G Elefanty, Gordon Keller

Nature Cell Biology | NATURE PUBLISHING GROUP | Published : 2015

Abstract

The generation of haematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) will depend on the accurate recapitulation of embryonic haematopoiesis. In the early embryo, HSCs develop from the haemogenic endothelium (HE) and are specified in a Notch-dependent manner through a process named endothelial-to-haematopoietic transition (EHT). As HE is associated with arteries, it is assumed that it represents a subpopulation of arterial vascular endothelium (VE). Here we demonstrate at a clonal level that hPSC-derived HE and VE represent separate lineages. HE is restricted to the CD34(+)CD73(-)CD184(-) fraction of day 8 embryoid bodies and it undergoes a NOTCH-dependent EHT to gener..

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Grants

Awarded by National Institutes of Health


Awarded by Canadian Institutes of Health Research


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Funding Acknowledgements

We would like to thank the SickKids-UHN Flow Cytometry Facility for their expert assistance with cell sorting, in particular A. Khandani,F.Xu at the Advanced Optical Microscopy Facility tor the great help with the time-lapse and confocal imaging, and S. Zandi for is with single-cell qRT-PCR. This work was supported by the National Institutes of Health grant U01 414100395 to G.K., SR00002303 to N.A.S. and by the Canadian Institutes of Health Research grants MOP93569 and EPS 127882 to G.K. Additional. support to A.D. and C.M.S. was provided by the Magna-Golftown Post-Doctoral Fellowship and the McMurrich Post-Doctoral Fellowship, respectively. A.G.E. and E.G.S. arc Senior Research Fellows at the National Health and Medical Research Council (NHMRC) of Australia. Their work was supported by Stem Cells Australia, the NHMRC and the Victorian Government's Operational Infrastructure Support Program.