Single-cell RNA sequencing analysis reveals the relationship of bone marrow and osteopenia in type 1 diabetic mice

Type 1 diabetes (T1D) is a multifactorial autoimmune disease characterized by the destruction of pancreatic beta (ß) cells and resultant hyperglycaemia. Broad knowledge about the genetics, epidemiology, and clinical management of T1D has been achieved, but the cell varieties in the bone marrow during T1D remain poorly understood. Here, we performed a single-cell RNA sequencing analysis of whole bone marrow cells from healthy (group C) and STZ-induced T1D (group D) mice for the first time, presenting a profile of the bone marrow cells and revealing the changes in immune cells in bone marrow. The bone marrow cells in both groups C and D were divided into 12 clusters, and there were 249 differentially expressed genes (DEGs). Compared with group C, the proportion of CD45+ immune cells in group D was not changed much. However, the diversity of CD45+ immune cells between groups C and D were greatly affected. There was a large increase in the proportion of bone marrow neutrophils (BM-neutrophils) and a large decrease in the proportion of B lymphocytes in group D. Furthermore, it was confirmed by X-ray and micro-CT analyses that osteopenia occurred in group D mice. Finally, we investigated the correlation between immune cells and osteopenia. The results of single-cell flow cytometry and correlation analysis showed that the ratio of BM-neutrophils/B lymphocytes was negatively correlated with osteopenia in T1D mice. Thus, precise regulation of the immune cells in the bone marrow may contribute to a better understanding of the treatment of T1D and the prevention of T1D-induced osteopenia. Overall design: Single-cell RNA sequencing analysis of bone marrow from normal and STZ-induced type 1 diabetic mice