Journal article
Differentiation of human embryonic stem cells to HOXA hemogenic vasculature that resembles the aorta-gonad-mesonephros
ES Ng, L Azzola, FF Bruveris, V Calvanese, B Phipson, K Vlahos, C Hirst, VJ Jokubaitis, QC Yu, J Maksimovic, S Liebscher, V Januar, Z Zhang, B Williams, A Conscience, J Durnall, S Jackson, M Costa, D Elliott, DN Haylock Show all
Nature Biotechnology | NATURE PUBLISHING GROUP | Published : 2016
DOI: 10.1038/nbt.3702
Abstract
The ability to generate hematopoietic stem cells from human pluripotent cells would enable many biomedical applications. We find that hematopoietic CD34+ cells in spin embryoid bodies derived from human embryonic stem cells (hESCs) lack HOXA expression compared with repopulation-competent human cord blood CD34+ cells, indicating incorrect mesoderm patterning. Using reporter hESC lines to track the endothelial (SOX17) to hematopoietic (RUNX1C) transition that occurs in development, we show that simultaneous modulation of WNT and ACTIVIN signaling yields CD34+ hematopoietic cells with HOXA expression that more closely resembles that of cord blood. The cultures generate a network of aorta-like ..
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Awarded by California Institute for Regenerative Medicine
Awarded by Arts of Baden-Wuerttemberg
Awarded by National Institutes of Health
Funding Acknowledgements
The assistance and cooperation of the Mercy Hospital for Women in the collection and provision of umbilical cord blood samples, and the expertise of M. Burton and P. Lau in the MCRI Flowcore facility, as well as FlowCore at Monash University, are gratefully acknowledged. The assistance of D. Cardozo with animal work is also gratefully acknowledged. This work was supported by grants from the Australian Stem Cell Centre, Stem Cells Australia, the Juvenile Diabetes Research Foundation, the National Health and Medical Research Council (NHMRC) of Australia, the California Institute for Regenerative Medicine (RT3-07761), the Stafford Fox Medical Research Foundation and the Victorian Government's Operational Infrastructure Support Program and Australian Government National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme (NHMRC IRIISS). The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government. A.G.E. and E.G.S. are supported as Senior Research Fellows of the NHMRC. Work in the laboratory of K.S.-L. was supported by grants from the Ministry of Science, Research and the Arts of Baden-Wuerttemberg (Az: 33-729.55-3/214-3, 33-729.55-312149). Work in the laboratory of H.K.A.M. was also supported by the National Institutes of Health (IR0113K100959-01A1).