Stepwise cell fate decision pathways during osteoclastogenesis at single-cell resolution

Area of Science:

• Cell Biology
• Molecular Biology
• Developmental Biology

Background:

• Osteoclasts are crucial for bone metabolism and pathological bone resorption.
• Osteoclast differentiation is stimulated by macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand.
• The precise molecular mechanisms governing osteoclast cell fate specification are not fully understood.

Discussion:

• This study presents a single-cell transcriptomic analysis of 7,228 murine cells during in vitro osteoclastogenesis.
• It details the stepwise molecular events involved in the osteoclast fate decision process.
• The findings reveal transient CD11c expression in osteoclast precursor cells.

Key Insights:

• Deletion of receptor activator of nuclear factor-κB in CD11c-expressing cells inhibits osteoclast formation.
• Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (Cited2) acts as a molecular switch for terminal osteoclast differentiation.
• In vivo deletion of Cited2 in osteoclast precursors prevents commitment to the osteoclast fate.

Outlook:

• This research provides a comprehensive molecular roadmap of osteoclast differentiation.
• It refines and expands the understanding of the molecular mechanisms driving osteoclastogenesis.
• Further investigation into Cited2's role could reveal therapeutic targets for bone diseases.