Evidence map›Paper›PMID 41576947›Full record

ArticleCell genomics2026

Spatial transcriptomics reveals altered communities and drivers of aberrant epithelia and pro-fibrotic fibroblasts in interstitial lung diseases.

Alok Jaiswal, Tristan Kooistra, Vladislav Pokatayev, Hélder N Bastos, Rita F Santos, Tresa R Sarraf, Åsa Segerstolpe, Crystal Lin, Liat Amir-Zilberstein, Shaina Twardus and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell genomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. ADAMTS14 is a novel modulator of fibroblast mechanoactivation in pulmonary fibrosis.American journal of respiratory and critical care medicine · 2026
    Article
  2. Review
  3. Article
  4. An NFATC4 phospho-switch links matrix stiffness to fibroblast fate.The Journal of clinical investigation · 2026
    Article
  5. Article
  6. Review
  7. 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

23 authors.

Alok JaiswalBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Tristan KooistraDivision of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Vladislav PokatayevBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Hélder N BastosDepartment of Pneumology, Hospital de São João, 4200-319 Porto, Portugal; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal; Faculty of Medicine/RISE-Health, University of Porto, 4200-319 Porto, Portugal.
Rita F Santosi3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal; School of Health Sciences - Polytechnic of Porto, 4200-072 Porto, Portugal.
Tresa R SarrafDivision of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Åsa SegerstolpeKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Crystal LinKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Liat Amir-ZilbersteinKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Shaina TwardusDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Kevin ShannonDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Shane P MurphyKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Rachel KnipeDivision of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Ingo K GanzlebenDivision of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Katharine E BlackDivision of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Toni M DeloreyKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Daniel B GrahamBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Yin P HungDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Lida P HaririDivision of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Jacques DeguineBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Agostinho CarvalhoLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, 4710-057 Braga/Guimarães, Portugal.
Benjamin D MedoffDivision of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Ramnik J XavierBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA 02114, USA; The Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: xavier@molbio.mgh.harvard.edu.

Funding

The importance of the IgG4 glycome in IgG4-related disease(s)U19AI110495 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI SHIV Subramaniam PILLAI · 2014 to 2026
$7.9M
Mapping Airway Epithelial Cell-Immune Cell Interactions in Lung Health and DiseaseU01HL175384 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Jacques Deguine, Benjamin David Medoff · 2024 to 2026
$2.3M
Targeting durotaxis in lung injury and fibrosisR01HL157384 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI MEDOFF, BENJAMIN DAVID · 2022 to 2025
$2.3M
Role of Intraepithelial airway macrophages in lung homeostasis and diseaseK08HL177151 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Tristan Gregory Kooistra · 2025 to 2026
$400k
NHLBI NIH HHS K08 HL177151NHLBI NIH HHS R01 HL157384NHLBI NIH HHS U01 HL175384NIAID NIH HHS U19 AI110495
6 · The paper itself

Abstract

Interstitial lung diseases (ILD) are characterized by fibrotic scarring of the lung parenchyma with remarkably unfavorable prognosis. Using single-nucleus RNA sequencing and spatial transcriptomics, we generated a comprehensive cellular network of the distal lung and its alterations in fibrosis. Integration with histopathology revealed that the transformation of normal parenchyma into fibrotic tissue is accompanied by ectopic bronchiolization and decellularization. Areas of active fibrosis were characterized by co-localization of pro-fibrotic CTHRC1-hi fibroblasts and aberrant transitional epithelial cells. We modeled this maladaptive differentiation of alveolar epithelial cells using organoids, demonstrating that all three pro-inflammatory ligands present in this pathogenic niche, TGF-β, IL-1β, and TNF-α, are jointly required for their induction. Additionally, we identified a requirement for the transcription factor NFATC4 during myofibroblast differentiation driven by soluble factors or mechanosensing. Collectively, this work identifies essential molecular drivers of the cellular interactions underlying lung fibrosis.

Indexed as

FibroblastsLung Diseases, InterstitialAnimalsCell DifferentiationEpithelial CellsHumansLungMiceMyofibroblastsPulmonary FibrosisSpatial TranscriptomicsTranscriptomeTransforming Growth Factor betaTransforming Growth Factor betaCTHRC1fibrosisidiopathic pulmonary fibrosisinflammatoninterstitial lung diseaselungmechanosensingmyofibroblastsingle-cellspatial transcriptomics

Identifiers

PMID41576947
PMCPMC12985369

What Socratic holds

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LicenceCC BY
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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 Socratic graph.