Single-cell and spatial transcriptomics approaches of the bone marrow microenvironment.

Area of Science:

• Hematology
• Stem Cell Biology
• Molecular Biology

Background:

• The bone marrow microenvironment contains hematopoietic and mesenchymal stem cells crucial for blood production and skeletal regeneration.
• Stem cell maintenance and differentiation are regulated by specific niches formed by signals from various bone marrow cell types.
• Recent advancements in single-cell and spatially resolved transcriptomics allow detailed characterization of the bone marrow microenvironment.

Purpose of the Study:

• To review recent findings on the murine bone marrow microenvironment using single-cell and spatially resolved transcriptomics.
• To summarize how these technologies have advanced our understanding of stem cell niches.
• To highlight the characterization of cell types and their roles in homeostasis, stress, and cancer remodeling.

Main Methods:

• Application of single-cell transcriptomics for systematic cell type identification.
• Utilizing spatially resolved transcriptomics to map cell localization and interactions.
• Label-free identification of bone marrow cell populations and their molecular profiles.

Main Results:

• Single-cell technologies enabled comprehensive, label-free identification and molecular/spatial characterization of bone marrow cells.
• Revealed significant transcriptional heterogeneity and novel subpopulations within previously assumed homogenous compartments.
• Identified Lepr Cxcl12-abundant reticular cells as major sources of prohematopoietic factors, with distinct subpopulations influencing niche formation.

Conclusions:

• Single-cell and spatial transcriptomics have clarified the molecular identity and localization of bone marrow cells.
• These approaches provide a foundation for deeper exploration of bone marrow niches in both mice and humans.
• Understanding these niches is critical for stem cell maintenance, differentiation, and tissue regeneration.