The role of <i>MXRA7</i> in bone marrow senescence involves macrophage polarization and microenvironment remodeling.

Marrow senescence contributes to overall organismal aging and involves functional alterations in both the mesenchymal and hematopoietic compartments of bone marrow. Although matrix remodeling-associated 7 (MXRA7) has been demonstrated to modulate mesenchymal function and megakaryocyte differentiation in mice, this study aimed to investigate the potential role of MXRA7 in marrow senescence. Single-cell RNA sequencing was performed on bone marrow cells from young and aged wild-type and MXRA7-knockout mice. Comparative analysis of 2-month-old and 2-year-old mice revealed that aging significantly altered the cellular proportions within the bone marrow niche, and MXRA7 deficiency markedly increased Macro1 macrophages in aged mice, likely driven by the dysregulation of the Ccl24-Ccr3 axis. MXRA7 deficiency altered Mid1 expression and the macrophage migration inhibitory factor (Cd74 + Cxcr4), Ccl6 + Ccr2, and Von Willebrand factor signaling pairs (Itga2b + Itgb3), all of which are closely associated with cell status in the bone marrow microenvironment. In summary, these findings underscore MXRA7's role in cellular profile shifts during bone marrow aging, offering novel insights into how MXRA7 coordinates hematopoietic and immune homeostasis in the bone marrow.