Evidence map›Paper›PMID 35657798›Full record

ArticlePloS one2022

Detection of infiltrating fibroblasts by single-cell transcriptomics in human kidney allografts.

Hemant Suryawanshi, Hua Yang, Michelle Lubetzky, Pavel Morozov, Mila Lagman, Gaurav Thareja, Alicia Alonso, Carol Li, Catherine Snopkowski, Aziz Belkadi and 10 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

18 citing papers in PubMed, 27 citations in OpenAlex.

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  7. Setdb1 ablation in macrophages attenuates fibrosis in heart allografts.Proceedings of the National Academy of Sciences of the United States of America · 2025
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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

20 authors at 4 institutions in 2 countries.

Hemant SuryawanshiLaboratory of RNA Molecular Biology, The Rockefeller University, New York, NY, United States of America.
Hua YangDivision of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, United States of America.
Michelle LubetzkyDivision of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, United States of America.
Pavel MorozovLaboratory of RNA Molecular Biology, The Rockefeller University, New York, NY, United States of America.
Mila LagmanDivision of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, United States of America.
Gaurav TharejaDepartment of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Doha, Qatar.ORCID 0000-0003-2277-6400
Alicia AlonsoEpigenomics Core Facility, Weill Cornell Medical College, New York, NY, United States of America.
Carol LiDivision of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, United States of America.
Catherine SnopkowskiDivision of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, United States of America.
Aziz BelkadiDepartment of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Doha, Qatar.
Franco B MuellerDivision of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, United States of America.
John R LeeDivision of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, United States of America.
Darshana M DadhaniaDivision of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, United States of America.
Steven P SalvatoreDivision of Renal Pathology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, United States of America.
Surya V SeshanDivision of Renal Pathology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, United States of America.
Vijay K SharmaDivision of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, United States of America.
Karsten SuhreDepartment of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Doha, Qatar.
Manikkam SuthanthiranDivision of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, United States of America.
Thomas TuschlLaboratory of RNA Molecular Biology, The Rockefeller University, New York, NY, United States of America.
Thangamani MuthukumarDivision of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, United States of America.ORCID 0000-0002-0294-6209
Cornell University · USNewYork–Presbyterian Hospital · USRockefeller University · USWeill Cornell Medical College in Qatar · QA

Funding

Clinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0M
Clinical and Translational Science CenterUL1TR000457 · NCATS · WEILL MEDICAL COLL OF CORNELL UNIV · PI IMPERATO-MCGINLEY, JULIANNE L · 2012 to 2016
$46.0M
Biomolecular Markers for Safe Minimization of ImmunosuppressionR37AI051652 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI SUTHANTHIRAN, MANIKKAM · 2009 to 2021
$4.7M
Urine mRNA Profiling for Renal Allograft SurveillanceR01AI051652 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI SUTHANTHIRAN, MANIKKAM · 2002 to 2006
$2.3M
Biomolecular Markers of Renal Allograft StatusK08DK087824 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI MUTHUKUMAR, THANGAMANI · 2011 to 2015
$658k
Noninvasive Biomarkers of Microcirculatory Injury in the Human Kidney AllograftR03DK105270 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI MUTHUKUMAR, THANGAMANI · 2016 to 2017
$170k
NCATS NIH HHS UL1 TR000457NCATS NIH HHS UL1 TR001873NIAID NIH HHS R01 AI051652NIAID NIH HHS R37 AI051652NIDDK NIH HHS K08 DK087824NIDDK NIH HHS R03 DK105270
6 · The paper itself

Abstract

We tested the hypothesis that single-cell RNA-sequencing (scRNA-seq) analysis of human kidney allograft biopsies will reveal distinct cell types and states and yield insights to decipher the complex heterogeneity of alloimmune injury. We selected 3 biopsies of kidney cortex from 3 individuals for scRNA-seq and processed them fresh using an identical protocol on the 10x Chromium platform; (i) HK: native kidney biopsy from a living donor, (ii) AK1: allograft kidney with transplant glomerulopathy, tubulointerstitial fibrosis, and worsening graft function, and (iii) AK2: allograft kidney after successful treatment of active antibody-mediated rejection. We did not study T-cell-mediated rejections. We generated 7217 high-quality single cell transcriptomes. Taking advantage of the recipient-donor sex mismatches revealed by X and Y chromosome autosomal gene expression, we determined that in AK1 with fibrosis, 42 months after transplantation, more than half of the kidney allograft fibroblasts were recipient-derived and therefore likely migratory and graft infiltrative, whereas in AK2 without fibrosis, 84 months after transplantation, most fibroblasts were donor-organ-derived. Furthermore, AK1 was enriched for tubular progenitor cells overexpressing profibrotic extracellular matrix genes. AK2, eight months after successful treatment of rejection, contained plasmablast cells with high expression of immunoglobulins, endothelial cell elaboration of T cell chemoattractant cytokines, and persistent presence of cytotoxic T cells. In addition to these key findings, our analysis revealed unique cell types and states in the kidney. Altogether, single-cell transcriptomics yielded novel mechanistic insights, which could pave the way for individualizing the care of transplant recipients.

Indexed as

Kidney DiseasesKidney TransplantationAllograftsFibroblastsFibrosisGraft RejectionHumansKidneyLiving DonorsTranscriptome

Identifiers

PMID35657798
PMCPMC9165878
OpenAlexW4281922323

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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.