Evidence map›Paper›PMID 38776915›Full record

ArticleMed (New York, N.Y.)2024

Cellular dynamics in pig-to-human kidney xenotransplantation.

Wanqing Pan, Weimin Zhang, Binghan Zheng, Brendan R Camellato, Jeffrey Stern, Ziyan Lin, Alireza Khodadadi-Jamayran, Jacqueline Kim, Philip Sommer, Karen Khalil and 11 more

Abstract read
In one paragraph

Article in Med (New York, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

30 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  16. Xenophagocytosis blockade enhances interspecies chimerism.bioRxiv : the preprint server for biology · 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

21 authors.

Wanqing PanGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
Weimin ZhangInstitute for Systems Genetics, NYU Langone Health, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Binghan ZhengGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Brendan R CamellatoInstitute for Systems Genetics, NYU Langone Health, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Jeffrey SternNYU Langone Transplant Institute, NYU Langone Health, New York, NY 10016, USA; Department of Surgery, NYU Grossman School of Medicine, New York, NY 10016, USA.
Ziyan LinApplied Bioinformatics Laboratories (ABL), NYU Grossman School of Medicine, New York, NY 10016, USA.
Alireza Khodadadi-JamayranApplied Bioinformatics Laboratories (ABL), NYU Grossman School of Medicine, New York, NY 10016, USA.
Jacqueline KimNYU Langone Transplant Institute, NYU Langone Health, New York, NY 10016, USA; Department of Surgery, NYU Grossman School of Medicine, New York, NY 10016, USA.
Philip SommerDepartment of Anesthesiology, Perioperative Care & Pain Medicine, NYU Langone Health, New York, NY 10016, USA.
Karen KhalilNYU Langone Transplant Institute, NYU Langone Health, New York, NY 10016, USA.
Elaina WeldonNYU Langone Transplant Institute, NYU Langone Health, New York, NY 10016, USA; Department of Surgery, NYU Grossman School of Medicine, New York, NY 10016, USA.
Jiangshan BaiGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Yinan ZhuInstitute for Systems Genetics, NYU Langone Health, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Peter MeynGenome Technology Center, NYU Grossman School of Medicine, New York, NY 10016, USA.
Adriana HeguyGenome Technology Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Pathology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Massimo MangiolaNYU Langone Transplant Institute, NYU Langone Health, New York, NY 10016, USA.
Adam GriesemerNYU Langone Transplant Institute, NYU Langone Health, New York, NY 10016, USA; Department of Surgery, NYU Grossman School of Medicine, New York, NY 10016, USA.
Brendan J KeatingInstitute for Systems Genetics, NYU Langone Health, New York, NY 10016, USA; NYU Langone Transplant Institute, NYU Langone Health, New York, NY 10016, USA; Department of Surgery, NYU Grossman School of Medicine, New York, NY 10016, USA; Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: brendan.keating@nyulangone.org.
Robert A MontgomeryNYU Langone Transplant Institute, NYU Langone Health, New York, NY 10016, USA; Department of Surgery, NYU Grossman School of Medicine, New York, NY 10016, USA. Electronic address: robert.montgomery@nyulangone.org.
Bo XiaGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Systems Genetics, NYU Langone Health, New York, NY 10016, USA; Society of Fellows, Harvard University, Cambridge, MA 02138, USA. Electronic address: xiabo@broadinstitute.org.
Jef D BoekeInstitute for Systems Genetics, NYU Langone Health, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA. Electronic address: jef.boeke@nyulangone.org.

Funding

Supplement for Center for Synthetic Regulatory Genomics: Building CACNA1C alleles associated with Neuropsychiatric DisordersRM1HG009491 · NHGRI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Jef D BOEKE · 2018 to 2026
$20.9M
Transposable Element Interaction and Its Impact on Human Development and HealthDP5OD033430 · OD · BROAD INSTITUTE, INC. · PI XIA, BO · 2022 to 2025
$1.9M
NHGRI NIH HHS RM1 HG009491NIH HHS DP5 OD033430
6 · The paper itself

Abstract

backgroundXenotransplantation of genetically engineered porcine organs has the potential to address the challenge of organ donor shortage. Two cases of porcine-to-human kidney xenotransplantation were performed, yet the physiological effects on the xenografts and the recipients' immune responses remain largely uncharacterized.

methodsWe performed single-cell RNA sequencing (scRNA-seq) and longitudinal RNA-seq analyses of the porcine kidneys to dissect xenotransplantation-associated cellular dynamics and xenograft-recipient interactions. We additionally performed longitudinal scRNA-seq of the peripheral blood mononuclear cells (PBMCs) to detect recipient immune responses across time.

findingsAlthough no hyperacute rejection signals were detected, scRNA-seq analyses of the xenografts found evidence of endothelial cell and immune response activation, indicating early signs of antibody-mediated rejection. Tracing the cells' species origin, we found human immune cell infiltration in both xenografts. Human transcripts in the longitudinal bulk RNA-seq revealed that human immune cell infiltration and the activation of interferon-gamma-induced chemokine expression occurred by 12 and 48 h post-xenotransplantation, respectively. Concordantly, longitudinal scRNA-seq of PBMCs also revealed two phases of the recipients' immune responses at 12 and 48-53 h. Lastly, we observed global expression signatures of xenotransplantation-associated kidney tissue damage in the xenografts. Surprisingly, we detected a rapid increase of proliferative cells in both xenografts, indicating the activation of the porcine tissue repair program.

conclusionsLongitudinal and single-cell transcriptomic analyses of porcine kidneys and the recipient's PBMCs revealed time-resolved cellular dynamics of xenograft-recipient interactions during xenotransplantation. These cues can be leveraged for designing gene edits and immunosuppression regimens to optimize xenotransplantation outcomes.

fundingThis work was supported by NIH RM1HG009491 and DP5OD033430.

Indexed as

Graft RejectionKidney TransplantationTransplantation, HeterologousAnimalsHeterograftsHumansKidneyLeukocytes, MononuclearRNA-SeqSequence Analysis, RNASingle-Cell AnalysisSwineantibody-mediated rejectioncell proliferationgenetic engineeringimmune responselongitudinal RNA-seqporcine kidneyscRNA-seqtissue repairTranslation to patientsxenotransplantation

Identifiers

PMID38776915
PMCPMC11317223

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.