Single-cell RNA Sequencing of Murine Islets Shows High Cellular Complexity at All Stages of Autoimmune Diabetes

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2020 Apr 7

PMID 32251514

Citations 62

Authors

Pavel N Zakharov

Hao Hu

Xiaoxiao Wan

Emil R Unanue

Affiliations

Soon will be listed here.

Abstract

Tissue-specific autoimmune diseases are driven by activation of diverse immune cells in the target organs. However, the molecular signatures of immune cell populations over time in an autoimmune process remain poorly defined. Using single-cell RNA sequencing, we performed an unbiased examination of diverse islet-infiltrating cells during autoimmune diabetes in the nonobese diabetic mouse. The data revealed a landscape of transcriptional heterogeneity across the lymphoid and myeloid compartments. Memory CD4 and cytotoxic CD8 T cells appeared early in islets, accompanied by regulatory cells with distinct phenotypes. Surprisingly, we observed a dramatic remodeling in the islet microenvironment, in which the resident macrophages underwent a stepwise activation program. This process resulted in polarization of the macrophage subpopulations into a terminal proinflammatory state. This study provides a single-cell atlas defining the staging of autoimmune diabetes and reveals that diabetic autoimmunity is driven by transcriptionally distinct cell populations specialized in divergent biological functions.

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