Evidence map›Paper›PMID 32362324›Full record

ArticleImmunity2020

Niche-Specific Reprogramming of Epigenetic Landscapes Drives Myeloid Cell Diversity in Nonalcoholic Steatohepatitis.

Jason S Seidman, Ty D Troutman, Mashito Sakai, Anita Gola, Nathanael J Spann, Hunter Bennett, Cassi M Bruni, Zhengyu Ouyang, Rick Z Li, Xiaoli Sun and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 283 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
283citing 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

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

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Precision pathophysiology in steatotic liver disease.Clinical and molecular hepatology · 2026
    Review
  8. [Alcohol liver disease: immunoregulatory mechanisms and precision therapeutic targets].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026
    Review
  9. Article
  10. Liver Macrophages in the Pathogenesis of Viral Hepatitis.Current issues in molecular biology · 2026
    Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Jason S SeidmanDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Ty D TroutmanDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Medicine, University of California, San Diego, La Jolla, CA, USA. Electronic address: ttroutman@health.ucsd.edu.
Mashito SakaiDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Anita GolaLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 201892, USA.
Nathanael J SpannDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Hunter BennettDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Cassi M BruniDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Zhengyu OuyangDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Rick Z LiDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Xiaoli SunDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA.
BaoChau T VuDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Martina P PasillasDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Kaori M EgoDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
David GosselinDepartment of Molecular Medicine, Université Laval, Quebec City, QC, Canada.
Verena M LinkDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Faculty of Biology, Division of Evolutionary Biology, Ludwig-Maximilian University of Munich, Munich, Germany.
Ling-Wa ChongGene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Ronald M EvansGene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA; Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Bonne M ThompsonCenter for Human Nutrition, UT Southwestern Medical Center, Dallas, TX, USA.
Jeffrey G McDonaldCenter for Human Nutrition, UT Southwestern Medical Center, Dallas, TX, USA.
Mojgan HosseiniDepartment of Pathology, University of California, San Diego, La Jolla, CA, USA.
Joseph L WitztumDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA.
Ronald N GermainLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 201892, USA.
Christopher K GlassDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Medicine, University of California, San Diego, La Jolla, CA, USA. Electronic address: ckg@ucsd.edu.

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Ye Zheng · 1985 to 2026
$82.8M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4M
Multiscale Analysis of Immune ResponsesZIAAI000545 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI GERMAIN, RONALD N · 2009 to 2025
$29.4M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007198 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C, INSEL, PAUL A · 1985 to 2024
$29.3M
Transcriptional GenomicsP01HL088093 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WITZTUM, JOSEPH L. · 2008 to 2018
$26.4M
SYNTHETIC SYSTEMSP50GM085764 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HASTY, JEFF M, IDEKER, TREY · 2010 to 2018
$23.3M
Contemporary Approaches to Cancer Cell Signaling and CommunicationT32CA009523 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DONOGHUE, DANIEL J, YANG, JING · 1985 to 2025
$12.1M
Transcriptional co-regulators and macrophage gene expressionR01DK091183 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLASS, CHRISTOPHER K · 2011 to 2025
$9.9M
Training Grant in GastroenterologyT32DK007202 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PRADIPTA · 1985 to 2022
$7.7M
EXPERIMENTAL ENDOCRINOLOGY AND METABOLISMT32DK007044 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Amit Majithia · 1986 to 2026
$4.6M
MOLECULAR BIOLOGICAL APPROACHES TO ENDOCRINOLOGYT32DK007541 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GAULTON, KYLE JEFFRIE, MAJITHIA, AMIT · 1987 to 2022
$4.5M
Regulation of Receptor Tyrosine KinasesR01GM065490 · NIGMS · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI DONOGHUE, DANIEL J · 2002 to 2005
$1.0M
NCI NIH HHS P30 CA014195NCI NIH HHS T32 CA009523NHLBI NIH HHS K99 HL148504NHLBI NIH HHS P01 HL088093NHLBI NIH HHS R21 HL088083NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK091183NIDDK NIH HHS T32 DK007044NIDDK NIH HHS T32 DK007202NIDDK NIH HHS T32 DK007541NIGMS NIH HHS P50 GM085764NIGMS NIH HHS R01 GM065490NIGMS NIH HHS T32 GM007198
6 · The paper itself

Abstract

Tissue-resident and recruited macrophages contribute to both host defense and pathology. Multiple macrophage phenotypes are represented in diseased tissues, but we lack deep understanding of mechanisms controlling diversification. Here, we investigate origins and epigenetic trajectories of hepatic macrophages during diet-induced non-alcoholic steatohepatitis (NASH). The NASH diet induced significant changes in Kupffer cell enhancers and gene expression, resulting in partial loss of Kupffer cell identity, induction of Trem2 and Cd9 expression, and cell death. Kupffer cell loss was compensated by gain of adjacent monocyte-derived macrophages that exhibited convergent epigenomes, transcriptomes, and functions. NASH-induced changes in Kupffer cell enhancers were driven by AP-1 and EGR that reprogrammed LXR functions required for Kupffer cell identity and survival to instead drive a scar-associated macrophage phenotype. These findings reveal mechanisms by which disease-associated environmental signals instruct resident and recruited macrophages to acquire distinct gene expression programs and corresponding functions.

Indexed as

Epigenesis, GeneticGene Expression RegulationAnimalsBiomarkersCellular MicroenvironmentCellular ReprogrammingChromatin Immunoprecipitation SequencingDietDisease Models, AnimalGene Expression ProfilingGene OntologyHigh-Throughput Nucleotide SequencingKupffer CellsMacrophagesMiceMyeloid CellsBiomarkersATF3ChIP-seqepigeneticsgenomicsKupffer cellLXRnonalcoholic steatohepatitisscRNA-seqtissue macrophageTREM2

Identifiers

PMID32362324
PMCPMC7305990

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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.