Evidence map›Paper›PMID 32669324›Full record

ArticleJournal of the American Society of Nephrology : JASN2020

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

Andrew F Malone, Haojia Wu, Catrina Fronick, Robert Fulton, Joseph P Gaut, Benjamin D Humphreys

Open access · bronzeAbstract read
In one paragraph

Article in Journal of the American Society of Nephrology : JASN, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
13.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

72 citing papers in PubMed, 109 citations in OpenAlex.

  1. Article
  2. Article
  3. Cell-cell crosstalk in kidney health and disease.Nature reviews. Nephrology · 2026
    Review
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  10. Review
  11. Donor-recipient mismatch at theScience translational medicine · 2025
    Article
  12. Article
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  15. Review
  16. Article
  17. RGMb drives macrophage infiltration to aggravate kidney disease.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  18. Article
  19. Review
  20. Article

12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Andrew F MaloneDivision of Nephrology, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
Haojia WuDivision of Nephrology, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
Catrina FronickMcDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
Robert FultonMcDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
Joseph P GautDepartment of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
Benjamin D HumphreysDivision of Nephrology, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, Missouri humphreysbd@wustl.edu.ORCID 0000-0002-6420-8703
Washington University in St. Louis · USJames S. McDonnell Foundation · US

Funding

WU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8M
Resource Based Center for Musculoskeletal Biology and Medicine (Overall Application)P30AR074992 · NIAMS · WASHINGTON UNIVERSITY · PI Simon Yue-Cheong Tang · 2019 to 2026
$6.8M
Understanding Myofibroblast Progenitor Fate and Function in Renal FibrosisR01DK103740 · NIDDK · WASHINGTON UNIVERSITY · PI BENJAMIN D. HUMPHREYS · 2015 to 2026
$3.9M
Adult Progenitors in Kidney TubulointerstitiumUH3DK107374 · NIDDK · WASHINGTON UNIVERSITY · PI HUMPHREYS, BENJAMIN D. · 2017 to 2019
$948k
Single Cell Analysis of Kidney Transplant Antibody Mediated RejectionK08DK120953 · NIDDK · WASHINGTON UNIVERSITY · PI MALONE, ANDREW FRANCIS · 2019 to 2023
$823k
Adult Progenitors in Kidney TubulointerstitiumUH2DK107374 · NIDDK · WASHINGTON UNIVERSITY · PI HUMPHREYS, BENJAMIN D. · 2015 to 2016
$626k
NCATS NIH HHS UL1 TR002345NIAMS NIH HHS P30 AR074992NIDDK NIH HHS K08 DK120953NIDDK NIH HHS R01 DK103740NIDDK NIH HHS UH2 DK107374NIDDK NIH HHS UH3 DK107374
6 · The paper itself

Abstract

backgroundIn 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.

methodsWhole-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.

resultsAnalysis 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 and recipient T cell clones within the rejecting kidney suggested lymphoid aggregation. The results indicate that donor-origin macrophages and T cells have distinct transcriptional profiles compared with their recipient counterparts, and that donor macrophages can persist for years post-transplantation.

conclusionsAnalysis of single nucleotide variants and their expression in single cells provides a powerful novel approach to accurately define leukocyte chimerism in a complex organ such as a transplanted kidney, coupled with the ability to examine transcriptional profiles at single-cell resolution.

Indexed as

Sequence Analysis, RNASingle-Cell AnalysisChimerismGenetic VariationGraft RejectionHumansKidney TransplantationLymphocyte SubsetsTissue DonorsTransplantation, Homologousgene expressiontranscriptional profilingtransplantation

Identifiers

PMID32669324
PMCPMC7461682
OpenAlexW3042998165

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.