<b>Supporting data for "Kat2a Regulates Expanded Potential in Mouse Embryonic Stem Cells by Increasing Transcriptional Heterogeneity".</b>

<p dir="ltr">Mouse embryonic stem cells (mESCs) are pluripotent cells derived from the inner cell mass of the blastocyst and have the potential to differentiate into all organs of the body. In contrast, mouse expanded potential stem cells (mEPSCs), originating from 8-cell stage embryos, possess the ability to differentiate into both embryonic and extraembryonic lineages <i>in vivo</i> and <i>in vitro</i>. Despite their remarkable capabilities, the underlying mechanisms of expanded potential in mEPSCs remain unknown. mEPSCs exhibit minimal WNT signaling activity, with higher levels of Axin1 expression. In this study, we utilized Axin1-overexpressed (OE) mESCs as a model to mimic mEPSCs-like features and discovered that Axin1 interacts with and downregulates Kat2a, a histone acetyltransferase. Additionally, we demonstrate that mESCs with Kat2a knockdown (KD) display expanded potential in both <i>in vivo</i> and <i>in vitro</i> settings. Mechanistically, Kat2a KD in mESCs promotes heterogeneous expression of some trophectoderm genes like <i>Gata2</i> through the downregulation of H3K9ac and upregulation of H3K4me3 at their promoter regions. These findings underscore the critical roles of the Axin1-Kat2a-H3K9ac axis in facilitating expanded potential in mESCs.</p>