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Activation of Wnt/β‐catenin signalling and HIF1α stabilisation alters pluripotency and differentiation/proliferation properties of human‐induced pluripotent stem cells
Author(s) -
Wei Hua,
Beeson Gyda C.,
Ye Zhiwei,
Zhang Jie,
Yao Hai,
Damon Brooke,
Morad Martin
Publication year - 2021
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1111/boc.202000055
Subject(s) - wnt signaling pathway , biology , induced pluripotent stem cell , microbiology and biotechnology , stem cell , gsk 3 , catenin , cancer research , signal transduction , embryonic stem cell , biochemistry , gene
Background Information Wnt/β‐catenin signalling, in the microenvironment of pluripotent stem cells (PSCs), plays a critical role in their differentiation and proliferation. Contradictory reports on the role of Wnt/β‐catenin signalling in PSCs self‐renewal and differentiation, however, render these mechanisms largely unclear. Results Wnt/β‐catenin signalling pathway in human‐induced pluripotent stem cells (hiPSCs) was activated by inhibiting glycogen synthase kinase 3 (GSK3), driving the cells into a mesodermal/mesenchymal state, exhibiting proliferative, invasive and anchorage‐independent growth properties, where over 70% of cell population became CD 44 (+)/CD133 (+). Wnt/β‐catenin signalling activation also altered the metabolic state of hiPSCs from aerobic glycolysis to oxidative metabolism and changed their drug and oxidative stress sensitivities. These effects of GSK3 inhibition were suppressed in HIF1α‐stabilised cells. Conclusions Persistent activation of Wnt/β‐catenin signalling endows hiPSCs with proliferative/invasive ‘teratoma‐like’ states, shifting their metabolic dependence and allowing HIF1α‐stabilisation to inhibit their proliferative/invasive properties. Significance The hiPSC potential to differentiate into ‘teratoma‐like’ cells suggest that stem cells may exist in two states with differential metabolic and drug dependency.