Long-term culture of human pluripotent stem cells (hPSCs) can lead to spontaneous mutations, genomic abnormalities, and alterations in gene expression, thereby compromising their self-renewal and pluripotency. Thus, optimizing the long-term culture conditions of hPSCs is crucial. In this study, we introduce O-cyclic phytosphingosine-1-phosphate (cP1P, Axceso Biopharma Co. Ltd.), a novel culture additive structurally analogous to S1P, which markedly enhances hPSC self-renewal and survival. Our results demonstrate that cP1P supplementation promotes long-term proliferation of hPSCs by upregulating pluripotency markers and maintaining their ability to differentiate into cell types derived from the three germ layers. Furthermore, RNA-seq analysis reveals that cP1P alleviates long-term culture-induced upregulation of apoptosis- and chordate embryonic development-related genes, while preventing the downregulation of stem cell maintenance pathways. Collectively, these findings suggest that cP1P effectively supports the proliferation, pluripotency, and differentiation potential of hPSCs during both short- and long-term cultures.
Woo et al. (2026) studied this question.