WNT3A promotes hematopoietic or mesenchymal differentiation from hESCs depending on the time of exposure

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 w...

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Bibliographic Details
Published in:Stem cell reports 2013, Vol.1 (1), p.53-65
Main Authors: Gertow, Karin, Hirst, Claire E, Yu, Qing C, Ng, Elizabeth S, Pereira, Lloyd A, Davis, Richard P, Stanley, Edouard G, Elefanty, Andrew G
Format: Article
Language:English
Subjects:
bone morphogenetic protein 4
Bone Morphogenetic Protein 4 - genetics
Bone Morphogenetic Protein 4 - metabolism
Cell Lineage
Cells, Cultured
Embryoid Bodies - cytology
Embryoid Bodies - metabolism
fat
Flt3 ligand
Glycogen Synthase Kinase 3 - antagonists & inhibitors
Hematopoiesis
Humans
interleukin 3
interleukin 6
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - metabolism
Mesoderm - cytology
Mesoderm - embryology
Mesoderm - metabolism
thrombopoietin
vasculotropin
Wnt Signaling Pathway
Wnt3a protein
Wnt3A Protein - antagonists & inhibitors
Wnt3A Protein - genetics
Wnt3A Protein - metabolism
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Summary: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 expressed genes associated with mesenchymal lineages. Mesospheres differentiated into cells with characteristics of bone, fat, and smooth muscle. These studies identify distinct effects for WNT3A, supporting the formation of hematopoietic or mesenchymal lineages from human embryonic stem cells, depending upon differentiation stage at the time of exposure.
ISSN:2213-6711
2213-6711
DOI:10.1016/j.stemcr.2013.04.002