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Lactylation of histone variant MacroH2A1 at K134 regulates osteogenic differentiation of bone marrow mesenchymal stem cells

GSE331389 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2026/05/24 Platform GPL29480
Summary
Osteoporosis, 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.
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Also filed as BioProject PRJNA1468002 and SRA study SRP701971. Searching any of these in the dataset finder brings you back here.

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