Reversible epiblast regionalisation determines differentiation potential of human PSCs [ATAC-seq]

The origins of these biases remain incompletely understood. In this study, we identify regional epiblast identity as the hallmark of differentiation competency through fluctuations in repressive and activating histone posttranslational modifications.

We present a novel approach to overcome this bias using a chemical chromatin restoration (CHR) treatment. This method restores transcriptional programs, chromatin accessibility, histone modification profiles, and differentiation potential, effectively recapitulating the competent anterior epiblast-like state. Furthermore, we propose that a high bivalency state is a defining feature of the anterior human epiblast and is a characteristic of unbiased PSCs.