Fine Tuning of Canonical Wnt Stimulation Enhances Differentiation of Pluripotent Stem Cells Independent of beta-Catenin-Mediated T-Cell Factor Signaling
Joseph Chen, Christian M Nefzger, Fernando J Rossello, Yu BY Sun, Sue Mei Lim, Xiaodong Liu, Suzan de Boer, Anja S Knaupp, Jinhua Li, Kathryn C Davidson, Jose M Polo, Tiziano Barberi
STEM CELLS | WILEY | Published : 2018
The canonical Wnt/β-catenin pathway is crucial for early embryonic patterning, tissue homeostasis, and regeneration. While canonical Wnt/β-catenin stimulation has been used extensively to modulate pluripotency and differentiation of pluripotent stem cells (PSCs), the mechanism of these two seemingly opposing roles has not been fully characterized and is currently largely attributed to activation of nuclear Wnt target genes. Here, we show that low levels of Wnt stimulation via ectopic expression of Wnt1 or administration of glycogen synthase kinase-3 inhibitor CHIR99021 significantly increases PSC differentiation into neurons, cardiomyocytes and early endodermal intermediates. Our data indica..View full abstract
Awarded by National Health and Medical Research Council of Australia (NHMRC)
Awarded by NHMRC
We are grateful for the high-quality cell sorting service and technical input provided by the Monash Flowcore Facility. Furthermore, the authors thank the ACRF Centre for Cancer Genomic Medicine at the MHTP Medical Genomics Facility for assistance with next generation library preparation and Illumina sequencing. X.L. is supported by the Monash Graduate Scholarship (MGS) and the International Postgraduate Research Scholarship (IPRS) from Monash University. S.B. is supported by the Australian Postgraduate Award (APA) and the International Postgraduate Research Scholarship (IPRS) from Monash University. J.M.P. is supported by a Silvia and Charles Senior Medical Viertel Fellowship, the Metcalf award from the National Stem Cell Foundation of Australia, and a National Health and Medical Research Council of Australia (NHMRC) project grant APP1051117. J.M.P. and T.B. are part of the ARC funded consortium Stem Cells Australia (T.B. former member). A.S.K. is supported by an NHMRC Early Career Fellowship APP1092280.