Journal article
WNT3A promotes hematopoietic or mesenchymal differentiation from hESCs depending on the time of exposure
K Gertow, CE Hirst, QC Yu, ES Ng, LA Pereira, RP Davis, EG Stanley, AG Elefanty
Stem Cell Reports | CELL PRESS | Published : 2013
Abstract
We investigated the role of canonical WNT signaling in mesoderm and hematopoietic development from human embryonic stem cells (hESCs) using a recombinant human protein-based differentiation medium (APEL). In contrast to prior studies using less defined culture conditions, we found that WNT3A alone was a poor inducer of mesoderm. However, WNT3A synergized with BMP4 to accelerate mesoderm formation, increase embryoid body size, and increase the number of hematopoietic blast colonies. Interestingly, inclusion of WNT3A or a GSK3 inhibitor in methylcellulose colony-forming assays at 4 days of differentiation abrogated blast colony formation but supported the generation of mesospheres that express..
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Awarded by Qatar National Research Fund
Funding Acknowledgements
The authors thank Robyn Mayberry and Amanda Bruce for provision of cells and Andrew Fryga and Darren Ellemor for flow cytometric sorting. This work was supported by the Australian Stem Cell Centre, Stem Cells Australia, the Juvenile Diabetes Research Foundation, the Qatar National Research Foundation, and the National Health and Medical Research Council (NHMRC) of Australia. E.G.S. and A.G.E. are Senior Research Fellows of the NHMRC. K. G. designed and performed experiments, collected, analyzed and interpreted data, made figures, and wrote the manuscript; L.A.P., E.S.N., C.E.H., and Q.C.Y. designed and performed experiments and made figures; R.P.D. contributed reagents and analytical tools; E. G. S. and A. G. E. designed experiments, collected, analyzed and interpreted data, made figures, provided financial support, and wrote the manuscript. A.G.E., E.G.S., and E.S.N. entered into consultancy agreements with STEMCELL Technologies after the completion of work in this manuscript. No support from the company was provided for these studies.