Single cell and spatial transcriptomics analysis of kidney double negative T lymphocytes in normal and ischemic mouse kidneys

Sepideh Gharaie; Kyungho Lee; Kathleen Noller; Emily K. Lo; Brendan Miller; Hyun Jun Jung; Andrea M. Newman-Rivera; Johanna T. Kurzhagen; Nirmish Singla; Paul A. Welling; Jean Fan; Patrick Cahan; Sanjeev Noel; Hamid Rabb

doi:10.1038/s41598-023-48213-2

Scientific Reports (Nov 2023)

Single cell and spatial transcriptomics analysis of kidney double negative T lymphocytes in normal and ischemic mouse kidneys

Sepideh Gharaie,
Kyungho Lee,
Kathleen Noller,
Emily K. Lo,
Brendan Miller,
Hyun Jun Jung,
Andrea M. Newman-Rivera,
Johanna T. Kurzhagen,
Nirmish Singla,
Paul A. Welling,
Jean Fan,
Patrick Cahan,
Sanjeev Noel,
Hamid Rabb

Affiliations

Sepideh Gharaie: Department of Medicine, Johns Hopkins University, School of Medicine
Kyungho Lee: Department of Medicine, Johns Hopkins University, School of Medicine
Kathleen Noller: Department of Biomedical Engineering, Johns Hopkins University, School of Medicine
Emily K. Lo: Department of Biomedical Engineering, Johns Hopkins University, School of Medicine
Brendan Miller: Department of Biomedical Engineering, Johns Hopkins University, School of Medicine
Hyun Jun Jung: Department of Medicine, Johns Hopkins University, School of Medicine
Andrea M. Newman-Rivera: Department of Medicine, Johns Hopkins University, School of Medicine
Johanna T. Kurzhagen: Department of Medicine, Johns Hopkins University, School of Medicine
Nirmish Singla: Department of Urology, Johns Hopkins University, School of Medicine
Paul A. Welling: Department of Medicine, Johns Hopkins University, School of Medicine
Jean Fan: Department of Biomedical Engineering, Johns Hopkins University, School of Medicine
Patrick Cahan: Department of Biomedical Engineering, Johns Hopkins University, School of Medicine
Sanjeev Noel: Department of Medicine, Johns Hopkins University, School of Medicine
Hamid Rabb: Department of Medicine, Johns Hopkins University, School of Medicine

DOI: https://doi.org/10.1038/s41598-023-48213-2
Journal volume & issue: Vol. 13, no. 1
pp. 1 – 13

Abstract

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Abstract T cells are important in the pathogenesis of acute kidney injury (AKI), and TCR+CD4-CD8- (double negative-DN) are T cells that have regulatory properties. However, there is limited information on DN T cells compared to traditional CD4+ and CD8+ cells. To elucidate the molecular signature and spatial dynamics of DN T cells during AKI, we performed single-cell RNA sequencing (scRNA-seq) on sorted murine DN, CD4+, and CD8+ cells combined with spatial transcriptomic profiling of normal and post AKI mouse kidneys. scRNA-seq revealed distinct transcriptional profiles for DN, CD4+, and CD8+ T cells of mouse kidneys with enrichment of Kcnq5, Klrb1c, Fcer1g, and Klre1 expression in DN T cells compared to CD4+ and CD8+ T cells in normal kidney tissue. We validated the expression of these four genes in mouse kidney DN, CD4+ and CD8+ T cells using RT-PCR and Kcnq5, Klrb1, and Fcer1g genes with the NIH human kidney precision medicine project (KPMP). Spatial transcriptomics in normal and ischemic mouse kidney tissue showed a localized cluster of T cells in the outer medulla expressing DN T cell genes including Fcer1g. These results provide a template for future studies in DN T as well as CD4+ and CD8+ cells in normal and diseased kidneys.

Published in Scientific Reports

ISSN: 2045-2322 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Medicine; Science
Website: https://www.nature.com/srep/

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