Single-cell RNA sequencing reveals transcriptomic profiles of pancreatic islet and infiltrating immune cells before the onset of type 1 diabetes

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Abstract Summary

Background: Type 1 diabetes (T1D) is characterised by autoimmune pancreatic beta cell destruction, resulting in insulin deficiency and hyperglycaemia. By the time of diagnosis, the autoimmune response has already destroyed many of the insulin-producing pancreatic beta cells, making it challenging to investigate the early phase of disease. This study used novel single-cell transcriptomic technology in a spontaneous model of T1D, the non-obese diabetic (NOD) mouse, to investigate the transcriptional profile of the variety of cells present in pancreatic islets prior to the onset of hyperglycaemia.

Methods: Pancreatic islets were purified from 10-12-week-old female NOD mice (n=10) prior to the onset of hyperglycaemia and from control 10-12 week-old B6 mice (n=2). After hand-picking and counting islets, a single-cell suspension was prepared from whole islet tissue. Bead-based 10X Genomics technology was used to prepare single-cell RNA-seq libraries, capturing 500-1000 islet cells per mouse. High-throughput sequencing was undertaken using HiSeq4000 at c.100k reads per cell. 

Results: The transcriptome of multiple pancreatic and infiltrating immune cell populations during the early stages of beta cell destruction was established, with detection of >2,000 transcripts per cell. Cells were grouped into distinct clusters based on their transcriptome, using a variety of single-cell analysis software including CellRanger. In NOD mouse islets, the transcriptome of approximately 1 in 3 cells was consistent with an immunological origin, including activated CD8+ lymphocytes, macrophages, dendritic cells and plasma cells. We also identified a subset of atypical pancreatic beta cells expressing immune response genes. This work, which allowed analysis of both the immune response and the beta cell response to the immune attack, demonstrates the potential of single-cell transcriptomics to reveal important new insights into the nature of early T1D.

Submission ID :
IDS54144
Submission Type
Abstract Topics
Royal Veterinary College and University of Oxford
University of Oxford
University of Oxford
University of Oxford

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IDS75126
Poster Session A
Poster and oral
Dr Michelle So
9 visits

KEY DATES

Event dates:
Thursday 25 October - Monday 29 October 2018

Abstract submission deadline:
Monday 14 May 2018

Abstract notification:
July 2018

Early registration deadline:
Monday 3 September 2018

Registration deadline:
Monday 15 October 2018

Contact
British Society for Immunology
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