Spatial transcriptomic interrogation of the murine bone marrow signaling landscape

Area of Science:

• Skeletal Biology
• Stem Cell Biology
• Genomics

Background:

• Skeletal stem and progenitor cells (SSPCs) self-renewal and differentiation are crucial for bone health.
• Dysregulation of SSPCs contributes to bone diseases.
• Understanding the bone marrow niche's role in regulating SSPCs is vital.

Purpose of the Study:

• To investigate the in vivo transcriptional landscape of SSPCs within their native bone marrow niche.
• To identify the cellular components and signaling networks governing SSPC regulation.
• To explore the spatial organization of SSPCs and their niche interactions.

Main Methods:

• Combined spatial transcriptomics and single-cell RNA sequencing (scRNAseq) in adult mouse femurs.
• Utilized a predictive modeling pipeline with deconvolution packages.
• Applied these techniques to fully mineralized bone tissue.

Main Results:

• Localized specific SSPC subtypes to distinct regions within the bone marrow niche.
• Identified key cellular players and signaling pathways within the niche microenvironment.
• Discovered spatially restricted signaling gradients from vasculature and bone surfaces influencing the niche.

Conclusions:

• Demonstrated the feasibility of spatial transcriptomics in mineralized tissues.
• Provided a comprehensive map of SSPC niches and their regulatory networks.
• Established a framework for understanding cell-cell communication and regulation of SSPCs in situ.