Department of Basic Medicine Sciences, and Department of Obstetrics of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
Department of Orthopedic, The Second Hospital of Shanxi Medical University, Taiyuan 030001, China.
J Adv Res. 2022 Nov;41:145-158. doi: 10.1016/j.jare.2022.01.006. Epub 2022 Jan 21.
Type 1 diabetes (T1D) is a multifactorial autoimmune disease. Broad knowledge about the genetics, epidemiology and clinical management of T1D has been achieved, but understandings about the cell varieties in the bone marrow during T1D remain limited.
We aimed to present a profile of the bone marrow cells and reveal the relationship of bone marrow and osteopenia in streptozotocin (STZ)-induced T1D mice.
The whole bone marrow cells from the femurs and tibias of healthy (group C) and STZ-induced T1D mice (group D) were collected for single-cell RNA sequencing analysis. Single-cell flow cytometry and immunohistochemistry were performed to confirm the proportional changes among bone marrow neutrophils (BM-neutrophils) (Cxcr2, Ly6g) and B lymphocytes (Cd19). X-ray and micro-CT were performed to detect bone mineral density. The correlation between the ratio of BM-neutrophils/B lymphocytes and osteopenia in STZ-induced T1D mice was analyzed by nonparametric Spearman correlation analysis.
The bone marrow cells in groups C and D were divided into 12 clusters, and 249 differentially expressed genes were found. The diversity of CD45 immune cells between groups C and D were greatly affected: the proportion of BM-neutrophils showed a significant increase while the proportion of B lymphocytes in group D showed a significant decrease. X-ray and micro-CT analyses confirmed that osteopenia occurred in group D mice. In addition, the results of single-cell flow cytometry and correlation analysis showed that the ratio of BM-neutrophils/B lymphocytes negatively correlated with osteopenia in STZ-induced T1D mice.
A single-cell RNA sequencing analysis revealed the profile and heterogeneity of bone marrow immune cells in STZ-induced T1D mice for the first time. The ratio of BM-neutrophils/B lymphocytes negatively correlated with osteopenia in STZ-induced T1D mice, which may enhance understanding for treating T1D and preventing T1D-induced osteopenia.
1 型糖尿病（T1D）是一种多因素自身免疫性疾病。人们已经对 T1D 的遗传学、流行病学和临床管理有了广泛的了解，但对 T1D 期间骨髓中的细胞种类仍了解有限。
我们旨在呈现骨髓细胞的特征，并揭示链脲佐菌素（STZ）诱导的 T1D 小鼠中骨髓与骨质疏松症的关系。
从健康（C 组）和 STZ 诱导的 T1D 小鼠（D 组）的股骨和胫骨的整个骨髓细胞中收集用于单细胞 RNA 测序分析。通过单细胞流式细胞术和免疫组织化学证实骨髓中性粒细胞（BM-中性粒细胞）（Cxcr2、Ly6g）和 B 淋巴细胞（Cd19）之间的比例变化。进行 X 射线和微 CT 检测以检测骨密度。通过非参数 Spearman 相关分析分析 STZ 诱导的 T1D 小鼠中 BM-中性粒细胞/B 淋巴细胞的比值与骨质疏松症之间的相关性。
C 组和 D 组的骨髓细胞分为 12 个簇，发现了 249 个差异表达基因。CD45 免疫细胞在 C 组和 D 组之间的多样性受到了极大的影响：BM-中性粒细胞的比例显著增加，而 D 组 B 淋巴细胞的比例显著下降。X 射线和微 CT 分析证实 D 组小鼠发生了骨质疏松症。此外，单细胞流式细胞术和相关分析的结果表明，BM-中性粒细胞/B 淋巴细胞的比值与 STZ 诱导的 T1D 小鼠的骨质疏松症呈负相关。
单细胞 RNA 测序分析首次揭示了 STZ 诱导的 T1D 小鼠骨髓免疫细胞的特征和异质性。BM-中性粒细胞/B 淋巴细胞的比值与 STZ 诱导的 T1D 小鼠的骨质疏松症呈负相关，这可能有助于治疗 T1D 和预防 T1D 诱导的骨质疏松症。
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