B3GALT5 knockout alters gycosphingolipid profile and facilitates transition to human naive pluripotency.

ABSTRACT: Conversion of human pluripotent stem cells from primed to naïve state is accompanied by altered transcriptome and methylome, but glycosphingolipid (GSL) profiles in naïve human embryonic stem cells (hESCs) have not been systematically characterized. Here we showed a switch from globo-(SSEA-3, SSEA-4, and Globo H) and lacto-series (fucosyl-Lc4Cer) to neolacto-series GSLs (SSEA-1 and H type 2 antigen), along with marked down-regulation of β-1,3-galactosyltransferase (B3GALT5) upon conversion to naïve state. CRISPR/Cas9-generated B3GALT5-knockout (KO) hESCs displayed an altered GSL profile, increased cloning efficiency and intracellular Ca²⁺, reminiscent of the naïve state, while retaining differentiation ability. The altered GSLs could be rescued through overexpression of B

SUBMITTER: Lin RJ 

PROVIDER: S-EPMC7959494 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature