A Map of Human Type 1 Diabetes Progression by Imaging Mass Cytometry
A Map of Human Type 1 Diabetes Progression by Imaging Mass Cytometry
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DOI：
10.1016/j.cmet.2018.11.014
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发表时间：
2019-03-05
期刊：
影响因子：
29
通讯作者：
Bodenmiller, Bernd
中科院分区：
文献类型：
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作者：
Damond, Nicolas;Engler, Stefanie;Bodenmiller, Bernd
1型糖尿病(T1D)是产生胰岛素的β细胞自身免疫破坏的结果。由于样本可获得性有限，无法纵向采样，以及缺乏支持全面组织分析的技术，因此缺乏对T1D开发期间变化的全面了解。在这里，我们使用成像质量细胞术(IMC)分析了来自12名人类捐赠者的1,581个胰岛，其中包括8个患有T1D的人。IMC能够以单细胞和空间分辨率同时测量35个生物标志物。我们从快照数据中通过T1D序列对胰岛进行伪时间分析，以重建胰岛β细胞丢失和绝缘炎的演变。我们的分析表明，在β细胞破坏之前，β细胞标志物的丢失以及细胞毒T细胞和辅助T细胞的招募。本文描述的方法证明了IMC对于提高我们对T1D发病机制的理解的价值，我们的数据为假说的产生和后续实验奠定了基础。
Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing beta cells. A comprehensive picture of the changes during T1D development is lacking due to limited sample availability, inability to sample longitudinally, and the paucity of technologies enabling comprehensive tissue profiling. Here, we analyzed 1,581 islets from 12 human donors, including eight with T1D, using imaging mass cytometry (IMC). IMC enabled simultaneous measurement of 35 biomarkers with single-cell and spatial resolution. We performed pseudotime analysis of islets through T1D progression from snapshot data to reconstruct the evolution of beta cell loss and insulitis. Our analyses revealed that beta cell destruction is preceded by a beta cell marker loss and by recruitment of cytotoxic and helper T cells. The approaches described herein demonstrate the value of IMC for improving our understanding of T1D pathogenesis, and our data lay the foundation for hypothesis generation and follow-on experiments.