TY - JOUR
T1 - WNT3A promotes hematopoietic or mesenchymal differentiation from hESCs depending on the time of exposure
AU - Gertow, Karin Astrid Maria
AU - Hirst, Claire Elizabeth
AU - Yu, Qing Cissy
AU - Ng, Elizabeth S S
AU - Pereira, Lloyd Ashley
AU - Davis, Richard Paul Frank
AU - Stanley, Edouard
AU - Elefanty, Andrew George
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://www.sciencedirect.com/science/article/pii/S2213671113000088
U2 - 10.1016/j.stemcr.2013.04.002
DO - 10.1016/j.stemcr.2013.04.002
M3 - Article
SN - 2213-6711
VL - 1
SP - 53
EP - 65
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 1
ER -