Evidence map›Paper›PMID 36324805›Full record

ArticlebioRxiv : the preprint server for biology2022

A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients.

Yered Pita-Juarez, Dimitra Karagkouni, Nikolaos Kalavros, Johannes C Melms, Sebastian Niezen, Toni M Delorey, Adam L Essene, Olga R Brook, Deepti Pant, Disha Skelton-Badlani and 53 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Review
  3. Loss of Heterozygosity and Its Importance in Evolution.Journal of molecular evolution · 2023
    Review
  4. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

63 authors at 7 institutions in 2 countries.

Yered Pita-JuarezDepartment of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Dimitra KaragkouniDepartment of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Nikolaos KalavrosDepartment of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Johannes C MelmsDepartment of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA.
Sebastian NiezenHarvard Medical School, Boston, MA, USA.
Toni M DeloreyKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Adam L EsseneDepartment of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Olga R BrookDepartment of Radiology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Deepti PantDepartment of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Disha Skelton-BadlaniHarvard Medical School, Boston, MA, USA.
Pourya NaderiDepartment of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Pinzhu HuangHarvard Medical School, Boston, MA, USA.
Liuliu PanNanoString Technologies, Inc., Seattle, WA, USA.
Tyler HetherNanoString Technologies, Inc., Seattle, WA, USA.
Tallulah S AndrewsAjmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
Carly G K ZieglerHarvard Medical School, Boston, MA, USA.
Jason ReevesNanoString Technologies, Inc., Seattle, WA, USA.
Andriy MyloserdnyyHarvard Medical School, Boston, MA, USA.
Rachel ChenHarvard Medical School, Boston, MA, USA.
Andy NamNanoString Technologies, Inc., Seattle, WA, USA.
Stefan PhelanNanoString Technologies, Inc., Seattle, WA, USA.
Yan LiangNanoString Technologies, Inc., Seattle, WA, USA.
Amit Dipak AminDepartment of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA.
Jana BiermannDepartment of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA.
Hanina HibshooshDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
Molly VereggeDepartment of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Zachary KramerDepartment of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Christopher JacobsDepartment of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Yusuf YalcinHarvard Medical School, Boston, MA, USA.
Devan PhillipsCurrent address: Genentech, 1 DNA Way, South San Francisco, CA, USA.
Michal SlyperCurrent address: Genentech, 1 DNA Way, South San Francisco, CA, USA.
Ayshwarya SubramanianKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Orr AshenbergKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Zohar Bloom-AckermannInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Victoria M TranInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
James GomezInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Alexander SturmInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Shuting ZhangInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Stephen J FlemingData Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sarah WarrenNanoString Technologies, Inc., Seattle, WA, USA.
Joseph BeechemNanoString Technologies, Inc., Seattle, WA, USA.
Deborah HungInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Mehrtash BabadiData Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Robert F PaderaDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Sonya A MacParlandAjmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
Gary D BaderDepartment of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Nasser ImadDepartment of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Isaac H SolomonDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Eric MillerNanoString Technologies, Inc., Seattle, WA, USA.
Stefan RiedelDepartment of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Caroline B M PorterKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Alexandra-Chloé VillaniBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Linus T-Y TsaiHarvard Medical School, Boston, MA, USA.
Winston HideDepartment of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Gyongyi SzaboHarvard Medical School, Boston, MA, USA.
Jonathan HechtDepartment of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Orit Rozenblatt-RosenKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Alex K ShalekHarvard Medical School, Boston, MA, USA.
Benjamin IzarDepartment of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA.
Aviv RegevKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Yury PopovHarvard Medical School, Boston, MA, USA.
Z Gordon JiangHarvard Medical School, Boston, MA, USA.
Ioannis S VlachosDepartment of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Broad Institute · USBeth Israel Deaconess Medical Center · USNanostring Technologies (United States) · USColumbia University Irving Medical Center · USBrigham and Women's Hospital · USUniversity Health Network · CAUniversity of Toronto · CA

Funding

Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3M
Transgenic CoreP30DK046200 · NIDDK · TUFTS MEDICAL CENTER · PI HU, FRANK B · 1992 to 2021
$25.0M
Systems Pharmacology of Therapeutic and Adverse Responses to ImmuneCheckpoint and Small Molecule DrugsU54CA225088 · NCI · HARVARD MEDICAL SCHOOL · PI HAIGIS, MARCIA · 2018 to 2022
$10.8M
Privileged and primitive hematopoietic stem cells, niches, and regulatory T cellsR01HL129506 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI FUJISAKI, JOJI · 2016 to 2025
$5.1M
Pan-Cancer characterization of 3’UTR somatic mutations controlling tumor immune evasionR01CA258776 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Ioannis Vlachos · 2022 to 2026
$2.9M
Mechanisms of liver metastasis and associated resistance to immunotherapyR37CA258829 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Benjamin Izar · 2021 to 2026
$2.6M
Dissecting mechanisms of immunotherapy resistance in melanoma patientsK08CA222663 · NCI · DANA-FARBER CANCER INST · PI IZAR, BENJAMIN · 2017 to 2021
$827k
Becton Dickinson LSR II Analytical Flow CytometerS10RR027050 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CLYNES, RAPHAEL A. · 2011 to 2011
$413k
Dissecting drug resistance in serial uveal melanoma biopsies using integrated, multi-modal single-cell profiling and novel machine learning tools.R21CA263381 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI IZAR, BENJAMIN · 2021 to 2022
$412k
NCI NIH HHS K08 CA222663NCI NIH HHS P30 CA013696NCI NIH HHS R01 CA258776NCI NIH HHS R21 CA263381NCI NIH HHS R37 CA258829NCI NIH HHS U54 CA225088NCRR NIH HHS S10 RR027050NHLBI NIH HHS R01 HL129506NIDDK NIH HHS P30 DK046200
6 · The paper itself

Abstract

The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. We identified hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells. Integrated analysis and comparisons with healthy controls revealed extensive changes in the cellular composition and expression states in COVID-19 liver, reflecting hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis. We also observed Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas, resembling similar responses in liver injury in mice and in sepsis, respectively. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition was dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells. Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.

Indexed as

COVID-19liverSARS-CoV-2single-cell sequencingsingle-nucleus sequencingspatial transcriptomics

Identifiers

PMID36324805
PMCPMC9628199
OpenAlexW4307482819

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.