GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE345nnn/GSE345877/suppl/GSE345877_P495_DE_table.xlsxftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE345nnn/GSE345877/suppl/GSE345877_P495_GO_GSEA.xlsxftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE345nnn/GSE345877/suppl/GSE345877_P495_GO_groups.xlsxftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE345nnn/GSE345877/suppl/GSE345877_P495_GO_enrichment.xlsxftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE345nnn/GSE345877/suppl/GSE345877_processed_data_readme.txtftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE345nnn/GSE345877/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE345877GEOGSEfalseImpact of Ndufs1 inactivation on the transcriptome of naïve-type mouse embryonic stem cells.Pluripotent embryonic stem cells (ESCs) possess unlimited proliferative potential and the capacity to develop all cell types of an organism. Mitochondrial metabolism is critically involved in the regulation of ESC self-renewal and differentiation, yet the specific role of the respiratory complex components in these processes remains largely unknown. Here, we demonstrate that while respiratory complex I (CI) function is dispensable for the ESC differentiation potential, its loss leads to a profound reduction in proliferation rates. Deficiency of the core CI subunit Ndufs1 induces mitochondrial reductive stress, characterized by a reduced mitochondrial NAD⁺/NADH ratio and elevated reactive oxygen species levels. The accumulation of mitochondrial NADH acts as a primary signal that negatively regulates ESC proliferation, associated with the activation of the integrated stress response and suppression of the NRF2/PGC-1α/SOD2 antioxidant axis. Our findings identify NADH-induced reductive stress as a critical checkpoint for ESC proliferation and propose that CI acts as a metabolic rheostat, calibrating ESC mitotic activity through mitochondrial-to-nuclear redox signaling.2026/09/17GSE345877GSM10018357GSM10018358GSM10018362GSM10018360GSM10018361GSM1001835924247345877Mus musculus