Poster Presentation CD1-MR1 2024

Mining single-cell RNA-seq datasets to map tissue-associated mucosal associated invariant T (MAIT) cells in health and disease (#230)

Christy Clutter 1 , Marco Marchetti 1 , Daniel Leung 1
  1. University of Utah, Salt Lake City, UTAH, United States

Background: Mucosal associated invariant T (MAIT) cells are known to be differentially activated, depleted and exhausted during metabolic disease (1). However, understanding their activity in such disease states is challenged by the difficulty of isolating them from human tissues, and the difficulty of animal models to fully recapitulate the human MAIT niche (2). In this study we sought to use in silico methods to mine existing single-cell RNAseq datasets to assess differential gene expression of tissue MAIT cells in health and metabolic disease.

­Methods: We defined MAIT cells according to previously published gene sets and applied this definition in silico to scRNAseq studies of the pancreas and liver. Our base definition included CD3+CD161+TRAV1-2+, with additional subsets defined according to Vorkas et al. (3). For clusters with the highest confidence of MAIT expression, we compared gene expression of MAIT cells between healthy and diabetic pancreas (4,5), and healthy and cirrhotic liver (6-8). 

Results: We were not able to identify a consistent MAIT cell presence in the pancreas, irrespective of disease state. In The liver, we identified several high-confidence MAIT cell clusters. Differential gene expression showed an upregulation of insulin like growth factor binding protein, mitochondrially derived humanin proteins, apolipoproteins and B cell regulatory genes such as CD40L in putative liver MAIT cells during cirrhosis.

Conclusions: We were able to identify putative MAIT cells across scRNAseq human tissue studies and compare gene expression between diseased and healthy states in the liver. We intend to expand this method as proof-of-principle to adipose and intestinal tissue, and conduct a tissue meta-analysis of MAIT cells in health and in metabolic disease.

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