Single-cell sequencing Unveils Age-Dependent Differential Impacts of Mxra7 Knockout on Mouse Bone Marrow Immune Cell Development and Function
Matrix remodeling associated 7 (Mxra7) belongs to the matrix remodeling-related gene family and is implicated in inflammatory neovascularization, liver injury, and autoimmune skin diseases. To elucidate the composition and transcriptional changes of bone marrow cells in Mxra7 knockout mice, we conducted single-cell RNA sequencing (scRNA-seq) in two-month-old and two-year-old mice. Our investigation revealed that Mxra7 knockout influences early B cell development and normal cell cycle functioning, impacting processes such as chromosome segregation and cell mitosis. Additionally, bone marrow B cells from knockout mice exhibited heightened differentiation potential compared to wild-type counterparts in aged mice. Mxra7 knockout initially suppressed basophil development at two months of age, only to yield an increased basophil proportation in two-year-old mice. Moreover, knockout mice exhibited elevated basophil numbers within bone marrow granulocytes. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated alterations in neurological disease-related functions in Mxra7 knockout bone marrow granulocytes. Cell communication analysis highlighted heightened quantity and quality of cellular interactions within bone marrow cells of knockout mice, notably enriching three inflammation-regulating signaling pathways. These findings underscore the pivotal role of Mxra7 in bone marrow immune cell development, with age-dependent effects on immune and inflammatory responses. Overall design: Comprehensive analysis of single-cell RNA-seq data revealed differences between two-month-old and two-year-old wild-type (WT) and Mxra7 knockout (KO) mice.