Harnessing Expressed Single Nucleotide Variation and Single Cell RNA Sequencing To Define Immune Cell Chimerism in the Rejecting Kidney Transplant.

Journal of the American Society of Nephrology : JASN
Andrew F MaloneBenjamin D Humphreys

Abstract

In solid organ transplantation, donor-derived immune cells are assumed to decline with time after surgery. Whether donor leukocytes persist within kidney transplants or play any role in rejection is unknown, however, in part because of limited techniques for distinguishing recipient from donor cells. Whole-exome sequencing of donor and recipient DNA and single-cell RNA sequencing (scRNA-seq) of five human kidney transplant biopsy cores distinguished immune cell contributions from both participants. DNA-sequence comparisons used single nucleotide variants (SNVs) identified in the exome sequences across all samples. Analysis of expressed SNVs in the scRNA-seq data set distinguished recipient versus donor origin for all 81,139 cells examined. The leukocyte donor/recipient ratio varied with rejection status for macrophages and with time post-transplant for lymphocytes. Recipient macrophages displayed inflammatory activation whereas donor macrophages demonstrated antigen presentation and complement signaling. Recipient-origin T cells expressed cytotoxic and proinflammatory genes consistent with an effector cell phenotype, whereas donor-origin T cells appeared quiescent, expressing oxidative phosphorylation genes. Finally, both donor...Continue Reading

References

Apr 11, 2001·American Journal of Clinical Pathology·I BittmannU Löhrs
Oct 3, 1953·Nature·R E BILLINGHAMP B MEDAWAR
Apr 13, 2004·Transplantation·Thomas E StarzlJohn J Fung
Aug 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·Thomas E Starzl
Dec 27, 2005·Transplantation·Kate R WyburnSteven J Chadban
Nov 26, 2008·Nature Reviews. Immunology·David M Mosser, Justin P Edwards
May 23, 2009·Science·Matthew G Vander HeidenCraig B Thompson
Dec 14, 2011·Current Opinion in Organ Transplantation·Roslyn B Mannon
Apr 17, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kerry A CaseyDavid Masopust
Dec 12, 2012·Annual Review of Immunology·Scott N MuellerWilliam R Heath
Sep 21, 2013·Nature Immunology·Luke C DaviesPhilip R Taylor
Jul 19, 2014·Immunity·Slava EpelmanGwendalyn J Randolph
Nov 15, 2014·International Reviews of Immunology·Kelley M Fracchia, Craig M Walsh
Apr 12, 2016·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·D K NayakT Mohanakumar
Jun 10, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Cora M L BeckersRichard J Pease
Dec 12, 2017·Nature Biotechnology·Hyun Min KangChun Jimmie Ye
Mar 31, 2018·Frontiers in Immunology·Cristina DumitruKevin J Maloy
Dec 15, 2018·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Ines G HarperGavin J Pettigrew
Mar 10, 2019·Science Immunology·Mark E SnyderDonna L Farber
Aug 14, 2019·Nature Reviews. Immunology·Nicole M ChapmanHongbo Chi
Apr 3, 2020·International Journal of Molecular Sciences·Line Aas MortensenHans Christian Beck

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Citations

Dec 15, 2020·Current Opinion in Organ Transplantation·Elly VarmaThangamani Muthukumar
Mar 14, 2021·Reviews in Endocrine & Metabolic Disorders·Adam StevensPhilip Murray
May 20, 2021·Transplantation·Edward B Thorp, Xunrong Luo
Jun 29, 2021·American Journal of Physiology. Renal Physiology·Kurt A ZimmermanJames F George
Jun 19, 2021·Journal of the American Society of Nephrology : JASN·Dries DeleersnijderBen Sprangers
Aug 15, 2021·Military Medical Research·Ying WangKonrad Fischer
Oct 12, 2021·Frontiers in Pharmacology·Erina SugitaHiroshi Itoh

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