GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE346nnn/GSE346145/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE346145GEOGSEfalseEzh2 Chromatin binding in Wild type mouse Embryonic Stem Cells (mESCs), β-actin Knock out mESC and upon rescue with a nuclear localization signal β-actinPluripotency and lineage commitment in embryonic stem cells depend on coordinated regulation of chromatin architecture and extracellular matrix (ECM) signaling. Here, we identify nuclear β-actin as a key regulator linking these processes in mouse embryonic stem cells. Loss of β-actin disrupts core pluripotency factors, including Oct4 and Sox2, and causes broad transcriptional changes, while nuclear re-expression rescues these defects. Chromatin accessibility analysis revealed reduced accessibility at regulatory regions of pluripotency genes, consistent with impaired chromatin remodeling. β-actin depletion also altered ECM-related gene expression, matrix properties, and cellular biomechanics, leading to impaired self-renewal, skewed lineage specification, and defective differentiation, particularly reduced neuronal potential and increased mesodermal-like fate bias. In vivo, β-actin loss restricted teratoma growth and compromised tri-lineage differentiation. Together, these results define nuclear β-actin as an important regulator of chromatin accessibility, ECM-dependent signaling, and stem cell fate.2026/09/09GSE346145GSM10025260GSM10025251GSM10025261GSM10025250GSM10025253GSM10025252GSM10025255GSM10025254GSM10025257GSM10025256GSM10025259GSM10025248GSM10025258GSM10025247GSM1002524924247346145Mus musculus