GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE331nnn/GSE331389/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE331389GEOGSEfalseLactylation of histone variant MacroH2A1 at K134 regulates osteogenic differentiation of bone marrow mesenchymal stem cellsOsteoporosis, a prevalent age-related bone disorder, stems from imbalanced osteoclast/osteoblast activity and skewed mesenchymal stem cell (MSC) lineage commitment. Although lactate is linked to osteoporosis pathogenesis, the role of protein lactylation in MSC osteogenic differentiation remains unelucidated. This experiment explored protein lactylation during early MSC osteogenic differentiation, focusing on histone variant MacroH2A1. Proteomics identified 375–318 lactylated proteins across undifferentiated, osteogenic differentiation Day 3 (OB3), and adipogenic differentiation Day 3 (AD3) MSCs; MacroH2A1 lactylation at lysine 134 (K134) was downregulated in OB3. MacroH2A1(K134Ala) mutation (disrupting lactylation) enhanced MSC osteogenesis. In ovariectomized mice, AAV-MacroH2A1(K134Ala) increased femoral trabecular bone mass and reduced marrow adipose tissue. This experiment demonstrates that MacroH2A1 K134 lactylation regulates MSC osteogenic commitment via epigenetic and transcriptional modulation, offering mechanistic insights and a potential therapeutic target for osteoporosis.2026/05/24GSE331389GSM9745130GSM9745131GSM9745129GSM9745126GSM9745127GSM9745128GSM9745132GSM974513329480331389Homo sapiens