Evidence map›Paper›PMID 38760586›Full record

ArticleNature medicine2024

Integrative multi-omics profiling in human decedents receiving pig heart xenografts.

Eloi Schmauch, Brian Piening, Maedeh Mohebnasab, Bo Xia, Chenchen Zhu, Jeffrey Stern, Weimin Zhang, Alexa K Dowdell, Jacqueline I Kim, David Andrijevic and 46 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
–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

41 citing papers in PubMed.

  1. Article
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  4. Large animal models of right heart failure due to pulmonary hypertension: a bridge to translational success.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
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  9. Article
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  14. Article
  15. Article
  16. Review
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  18. Lung rehabilitation using xenogeneic cross-circulation does not lead to hyperacute rejection in a human lung transplantation model.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2025
    Article
  19. Review
  20. Article
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

56 authors.

Eloi Schmauch *Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Brian Piening *Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, USA.ORCID 0000-0002-2683-8157
Maedeh Mohebnasab *Division of Molecular Genetics Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.ORCID 0000-0001-6623-9514
Bo Xia *Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-0929-7253
Chenchen Zhu *Department of Genetics, Stanford University, Stanford, CA, USA.
Jeffrey Stern *NYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.ORCID 0000-0001-5588-0357
Weimin Zhang *Institute for Systems Genetics, NYU Langone Health, New York, NY, USA.ORCID 0000-0002-8836-1438
Alexa K DowdellEarle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, USA.ORCID 0000-0003-4866-6293
Jacqueline I KimNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.ORCID 0000-0001-8165-525X
David AndrijevicDepartment of Surgery, NYU Grossman School of Medicine, New York, NY, USA.ORCID 0000-0002-5703-3837
Karen KhalilNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.ORCID 0000-0001-7350-0418
Ian S JaffeNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.ORCID 0000-0002-7309-308X
Bao-Li LozaPenn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA.
Loren GragertDivision of Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Brendan R CamellatoInstitute for Systems Genetics, NYU Langone Health, New York, NY, USA.
Michelli F Oliveira10x Genomics, Pleasanton, CA, USA.
Darragh P O'BrienNuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID 0000-0003-4924-7795
Han M ChenDepartment of Medicine, NYU Grossman School of Medicine, New York, NY, USA.ORCID 0009-0001-8124-5792
Elaina WeldonNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Hui GaoPenn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA.
Divya GandlaPenn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA.
Andrew ChangPenn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0009-0005-5254-9593
Riyana BhattPenn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA.
Sarah GaoPenn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA.
Xiangping LinDepartment of Genetics, Stanford University, Stanford, CA, USA.ORCID 0000-0001-6045-4459
Kriyana P ReddyPenn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA.
Larisa KagermazovaInstitute for Systems Genetics, NYU Langone Health, New York, NY, USA.
Alawi H HabaraDepartment of Biochemistry, College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.ORCID 0000-0002-5384-8764
Sophie WidawskyNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Feng-Xia LiangDART Microscopy Laboratory, NYU Langone Health, New York, NY, USA.ORCID 0000-0003-0037-4590
Joseph SallDART Microscopy Laboratory, NYU Langone Health, New York, NY, USA.
Alexandre LoupyUniversité Paris Cité, Paris Institute for Transplantation and Organ Regeneration, Paris, France.
Adriana HeguyGenome Technology Center, NYU Langone Health, New York, NY, USA.ORCID 0000-0002-2836-6683
Sarah E B Taylor10x Genomics, Pleasanton, CA, USA.
Yinan ZhuDivision of Molecular Genetics Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Basil MichaelDepartment of Genetics, Stanford University, Stanford, CA, USA.ORCID 0000-0003-4009-0912
Lihua JiangDepartment of Genetics, Stanford University, Stanford, CA, USA.
Ruiqi JianDepartment of Genetics, Stanford University, Stanford, CA, USA.
Anita S ChongDepartment of Surgery, The University of Chicago, Chicago, IL, USA.
Robert L FairchildDepartment of Inflammation and Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Suvi Linna-KuosmanenBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-3278-2727
Minna U KaikkonenA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.ORCID 0000-0001-6294-0979
Vasishta TatapudiNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Marc LorberUnited Therapeutics, Silver Spring, MD, USA.
David AyaresRevivicor, Blacksburg, VA, USA.
Massimo MangiolaNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Navneet NarulaNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Nader MoazamiNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.ORCID 0000-0001-5306-070X
Harvey PassNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Ramin S HeratiDepartment of Medicine, NYU Grossman School of Medicine, New York, NY, USA.ORCID 0000-0003-2613-4050
Adam GriesemerNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.ORCID 0000-0003-4894-2024
Manolis Kellis *Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-7113-9630
Michael P Snyder *Department of Genetics, Stanford University, Stanford, CA, USA.ORCID 0000-0003-0784-7987
Robert A Montgomery *NYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Jef D Boeke *Institute for Systems Genetics, NYU Langone Health, New York, NY, USA.ORCID 0000-0001-5322-4946
Brendan J Keating *Institute for Systems Genetics, NYU Langone Health, New York, NY, USA. brendan.keating@nyulangone.org.ORCID 0000-0002-3320-3723

Funding

Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MARK Reid PHILIPS · 1985 to 2026
$83.1M
Multi-omic Biomarker Discovery and Validation in Heart Transplant Patient PopulationsR01AI144522 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DENG, MARIO C., KEATING, BRENDAN JAMES · 2020 to 2024
$4.0M
NCI NIH HHS P30 CA016087NIAID NIH HHS R01 AI144522
6 · The paper itself

Abstract

In a previous study, heart xenografts from 10-gene-edited pigs transplanted into two human decedents did not show evidence of acute-onset cellular- or antibody-mediated rejection. Here, to better understand the detailed molecular landscape following xenotransplantation, we carried out bulk and single-cell transcriptomics, lipidomics, proteomics and metabolomics on blood samples obtained from the transplanted decedents every 6 h, as well as histological and transcriptomic tissue profiling. We observed substantial early immune responses in peripheral blood mononuclear cells and xenograft tissue obtained from decedent 1 (male), associated with downstream T cell and natural killer cell activity. Longitudinal analyses indicated the presence of ischemia reperfusion injury, exacerbated by inadequate immunosuppression of T cells, consistent with previous findings of perioperative cardiac xenograft dysfunction in pig-to-nonhuman primate studies. Moreover, at 42 h after transplantation, substantial alterations in cellular metabolism and liver-damage pathways occurred, correlating with profound organ-wide physiological dysfunction. By contrast, relatively minor changes in RNA, protein, lipid and metabolism profiles were observed in decedent 2 (female) as compared to decedent 1. Overall, these multi-omics analyses delineate distinct responses to cardiac xenotransplantation in the two human decedents and reveal new insights into early molecular and immune responses after xenotransplantation. These findings may aid in the development of targeted therapeutic approaches to limit ischemia reperfusion injury-related phenotypes and improve outcomes.

Indexed as

Heart TransplantationHeterograftsTransplantation, HeterologousAnimalsFemaleGene Expression ProfilingGraft RejectionHumansLeukocytes, MononuclearLipidomicsMaleMetabolomicsMultiomicsProteomicsReperfusion InjurySwine

Identifiers

PMID38760586

What OpenQuestion holds

Textmetadata
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.