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• W2469473718 abstract "Human embryonic stem cells (hESCs) closely resemble mouse epiblast stem cells exhibiting primed pluripotency unlike mouse ESCs (mESCs), which acquire a na€ ive pluripotent state. Efforts have been made to trigger na€ ive pluripotency in hESCs for subsequent unbiased lineage-specific differentiation, a common conundrum faced by primed pluripotent hESCs due to heterogeneity in gene expression existing within and between hESC lines. This required either ectopic expres- sion of na€ ive genes such as NANOG and KLF2 or inclusion of multiple pluripotency-associated factors. We report here a novel combination of small molecules and growth factors in culture medium (2i/LIF/basic fibroblast growth factor 1 Ascorbic Acid 1 Forskolin) facilitating rapid induction of transgene-free na€ ive pluripotency in hESCs, as well as in mESCs, which has not been shown earlier. The converted na€ ive hESCs survived long-term single-cell passaging, main- tained a normal karyotype, upregulated na€ ive pluripotency genes, and exhibited dependence on signaling pathways similar to na€ ive mESCs. Moreover, they undergo global DNA demethylation and show a distinctive long noncoding RNA profile. We propose that in our medium, the FGF signaling pathway via PI3K/AKT/mTORC induced the conversion of primed hESCs toward na€ ive pluripotency. Collectively, we demonstrate an alternate route to capture na€ ive pluripotency in hESCs that is fast, reproducible, supports na€ ive mESC derivation, and allows efficient differentia- tion. STEM CELLS 2015;00:000-000 SIGNIFICANCE STATEMENT" @default.
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• W2469473718 date "2015-01-01" @default.
• W2469473718 modified "2023-09-27" @default.
• W2469473718 title "Alternative Routes to Induce Na€ ive Pluripotency in Human Embryonic Stem Cells" @default.
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