Deep transcriptome profiling revealed LIF-gp130-mediated signaling in naive pluripotency

Naive pluripotency, characteristic of early embryonic cells, remains incompletely understood, particularly in its functional and transcriptional heterogeneity. This study investigates the role of LIF-gp130-mediated signaling in relation to the heterogeneity of naive pluripotency in mouse embryonic stem cells (mESCs). Through deep transcriptome profiling of mESCs under different conditions using cap analysis gene expression sequencing (CAGE-seq), we identified significant diversity in the expression of pluripotency markers. To investigate the effects of LIF signaling, we generated gp130 (Y757F) mutant ESCs, which exhibited reduced ERK phosphorylation and more uniform Nanog expression, thereby reducing cellular heterogeneity. Our analysis revealed novel transcription start sites and transcribed enhancers specific to naive pluripotency states. These findings highlight the importance of the LIFR-gp130-pERK axis in modulating naive pluripotent states and provide insights that further our understanding of naive pluripotency.