GSE110805
Reduced MEK inhibition confers a growth advantage and reduces genomic instability in naïve human ES cells (RNA-seq data set)
Human embryonic stem cells (hESCs) can be captured in either a primed state resembling the post-implantation epiblast or in a naïve state resembling the pre-implantation epiblast. Naïve culture conditions allow study of pre-implantation development ex vivo but reportedly lead to chromosomal abnormalities, compromising their utility in research and potential therapeutic applications. Although MEK inhibition is essential for the naïve state, here we show that reduced MEK inhibition facilitates the establishment and maintenance of naïve hESCs that retain naïve-specific transcriptional and DNA methylation patterns yet accrue fewer chromosomal abnormalities. We further show that hESCs cultured under these modified conditions are less prone to apoptosis and proliferate more rapidly. Our results point to the importance of residual MAPK signaling and provide a simple modification to current protocols to enable robust growth and genomic stability in naïve hESCs. Overall design: RNA-seq