Pluto Bioinformatics

GSE105164: Wnt inhibition confers hESCs a unique transcriptional state compatible with differentiation, but not with derivation

Bulk RNA sequencing

Human embryonic stem cells (hESCs) hold great value for future clinical applications. However, standard culture conditions maintain hESCs in a primed state, which bears heterogeneity and a tendency for spontaneous differentiation. To counter these drawbacks, hESCs have been converted to a naive state, but this has in turn restricted the efficiency of existing directed differentiation protocols. We show that adaptation of hESCs to Wnt-inhibiting condition (Wnt-i) conferred a unique transcriptional signature with high levels of pluripotency markers and reduced levels of differentiation markers. Moreover, neuronal and cardiac differentiation of Wnt-i hESCs progressed similarly to primed hESCs, unlike their nave counterparts. Remarkably, in contrast to mouse, Wnt-i conditions failed to support direct derivation of hESCs, suggesting that active Wnt signaling is required for the transition from inner cell mass to hESCs. Wnt-i hESCs retained advantages of both primed and naive counterparts and may therefore be a better starting point for differentiation towards clinically desired cell types. SOURCE: Laurentijn Tilleman Ghent University

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