Identification of Critical Molecular Pathways Induced by HDAC11 Overexpression in Cardiac Mesenchymal Stem Cells

HDAC11, the only class IV histone deacetylase, primarily functions as a fatty acid deacylase and has been implicated in metabolic regulation, cancer stemness, and muscle regeneration. However, its role in cardiac mesenchymal stem cells (CMSCs) remains unexplored. To investigate the effects of HDAC11 overexpression on the gene regulatory networks in CMSCs, we treated mouse CMSCs with an adenoviral vector encoding human HDAC11 (Ad-HDAC11) versus adenoviral GFP (Ad-GFP) as a control. Gene expression and pathway enrichment were assessed using RNA sequencing (RNA-seq), and HDAC11 overexpression was validated at the RNA and protein levels through qRT-PCR and Western blot. RNA-seq and Gene Ontology (GO) analysis revealed that HDAC11 overexpression activated cell cycle pathways while suppressing nucleotide transport and phagolysosome-related processes. Furthermore, pHH3 protein level was increased, suggested enhanced proliferation in HDAC11-overexpressed CMSCs. qRT-PCR also confirmed the downregulation of GM11266, a long non-coding RNA, in HDAC11-overexpressing CMSCs. In summary, HDAC11 overexpression promotes transcriptional reprogramming, cell cycle progression, and CMSC proliferation, underscoring its potential role in regulating CMSC growth and division.