A novel culture system robustly maintained pluripotency of embryonic stem cells and accelerated somatic reprogramming by activating Wnt signaling.

ABSTRACT

Wnt signaling is intrinsic to embryonic stem cell self-renewal and mammalian development. However, the effects of wnts on ES cells self-renewal and iPS cells transduction was not clearly understood. In this study, L-Wnt3a cells that secreted activated Wnt3a protein into medium were used to produce Wnt3a condition medium (Wnt3a-CM) or feeder layer for ES cells cultivation and iPS cells transduction. The results showed that L-Wnt3a cells as feeder layer significantly promoted establishment of ES cell lines and generation of iPS cells. The ES cells robustly maintained pluripotency in Wnt3a-CM on feeder free condition. Moreover, we demonstrate that activated Wnt signaling by Wnt3a-CM at the early stage of reprogramming promoted generation of iPS cells by up-regulating Tcf3 and Tcf4, improving mesenchymal-to-epithelial transition (MET), promptly reactivating endogenous pluripotent genes, and regulating epigenetic remodeling. Taken together, L-Wnt3a cells and their condition medium could be a novel culture system to robustly maintained pluripotency of ES cells and accelerated somatic reprogramming by activating Wnt signaling.