Microbiota regulates bone marrow mesenchymal stem cell lineage differentiation and immunomodulation

Area of Science:

• Microbiology
• Stem Cell Biology
• Immunology

Background:

• The mammalian microbiota, a key external microenvironment, regulates numerous organ systems.
• The role of microbiota in maintaining skeletal system and bone marrow mesenchymal stem cell (BMMSC) homeostasis remains largely unknown.

Purpose of the Study:

• To investigate the influence of the gut microbiota on the homeostasis of bone marrow mesenchymal stem cells (BMMSCs).
• To determine if microbiota colonization restores BMMSC function in germ-free mice.

Main Methods:

• Utilized germ-free (GF) mouse models colonized with specific-pathogen-free (SPF) microbiota (conventionalized, ConvD).
• Assessed BMMSC stemness, proliferation, and differentiation capabilities.
• Evaluated BMMSC immunomodulatory functions, including T-cell apoptosis and cytokine secretion.
• Used single-cell RNA-sequencing to analyze gene expression patterns.

Main Results:

• GF-derived BMMSCs exhibited significantly altered stemness compared to SPF-derived BMMSCs.
• Conventionalization (ConvD) normalized the proliferation and differentiation abilities of BMMSCs.
• Normal microbiota is essential for maintaining BMMSC immunomodulatory properties, including T-cell apoptosis induction.
• GF-derived BMMSCs failed to ameliorate experimental colitis, unlike ConvD BMMSCs.
• Single-cell RNA-sequencing revealed distinct gene expression patterns between GF and ConvD/SPF BMMSCs.

Conclusions:

• The gut microbiota critically regulates BMMSC stemness and function.
• Microbiota colonization restores BMMSC homeostasis and immunomodulatory capacity.
• These findings highlight the intricate connection between the gut microbiota and skeletal health.