Evidence map›Paper›PMID 39901013›Full record

ArticleNature genetics2025

Spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis.

Annika Vannan, Ruqian Lyu, Arianna L Williams, Nicholas M Negretti, Evan D Mee, Joseph Hirsh, Samuel Hirsh, Niran Hadad, David S Nichols, Carla L Calvi and 15 more

Abstract read
In one paragraph

Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.

0numbers the graph read from it
0cells of the map it votes in
107citing 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

107 citing papers in PubMed.

  1. Article
  2. Targeting the CD4Molecular biomedicine · 2026
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47 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Annika Vannan *Division of Bioinnovation and Genome Sciences, Translational Genomics Research Institute, Phoenix, AZ, USA.ORCID http://orcid.org/0000-0001-7796-5597
Ruqian Lyu *St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
Arianna L WilliamsDivision of Bioinnovation and Genome Sciences, Translational Genomics Research Institute, Phoenix, AZ, USA.ORCID http://orcid.org/0009-0002-2725-0221
Nicholas M NegrettiDivision of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0003-1022-8650
Evan D MeeDivision of Bioinnovation and Genome Sciences, Translational Genomics Research Institute, Phoenix, AZ, USA.
Joseph HirshDivision of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0009-0004-0457-5503
Samuel HirshDivision of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0009-0009-8819-5984
Niran HadadDivision of Bioinnovation and Genome Sciences, Translational Genomics Research Institute, Phoenix, AZ, USA.
David S NicholsDivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Carla L CalviDivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Chase J TaylorDivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-7942-0483
Vasiliy V PolosukhinDivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Ana P M SerezaniDivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
A Scott McCallDivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Jason J GokeyDivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Heejung ShimMelbourne Integrative Genomics, University of Melbourne, Parkville, Victoria, Australia.
Lorraine B WareDivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-9429-4702
Matthew J BacchettaDepartment of Cardiac Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0003-4456-4484
Ciara M ShaverDivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Timothy S BlackwellDivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Rajat WaliaDepartment of Thoracic Disease and Transplantation, Norton Thoracic Institute, Phoenix, AZ, USA.ORCID http://orcid.org/0000-0001-5036-2921
Jennifer M S SucreDivision of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.
Jonathan A KropskiDivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-8923-1344
Davis J McCarthySt. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.ORCID http://orcid.org/0000-0002-2218-6833
Nicholas E BanovichDivision of Bioinnovation and Genome Sciences, Translational Genomics Research Institute, Phoenix, AZ, USA. nbanovich@tgen.org.ORCID http://orcid.org/0000-0003-2604-3247

Funding

Mechanisms of Familial Pulmonary FibrosisP01HL092870 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BLACKWELL, TIMOTHY S. · 2010 to 2020
$21.6M
Project 4: Defining the Molecular Natural History of Early and Progressive Pulmonary FibrosisP01HL172729 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Margaret Louise Salisbury · 2024 to 2026
$11.2M
Interdisciplinary Training Program in Lung ResearchT32HL094296 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Ray Stokes Peebles · 2008 to 2026
$6.3M
Spatiotemporal genomic regulation of disease initiation and progression in pulmonary fibrosisR01HL145372 · NHLBI · TRANSLATIONAL GENOMICS RESEARCH INST · PI Nicholas Eli Banovich, Jonathan Andrew Kropski · 2019 to 2026
$6.0M
Immunogenomic analysis of donor lung injury and its impact on clinical outcomes after lung transplantationR01HL160551 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Ciara M Shaver · 2022 to 2026
$3.4M
Integrated analysis of multi-omic QTLs at single cell resolutionR01HG011886 · NHGRI · TRANSLATIONAL GENOMICS RESEARCH INST · PI BANOVICH, NICHOLAS ELI · 2022 to 2025
$2.9M
The GOLD Study: Goal of Open Lung Ventilation in DonorsR01HL126176 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WARE, LORRAINE B · 2015 to 2020
$2.8M
Integrated Molecular and Cellular Drivers of AlveologenesisR01HL168556 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jennifer MalcolmSrygley Sucre · 2023 to 2026
$2.8M
Unraveling the molecular origins of chronic parenchymal lung diseasesU01HL175444 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Nicholas Eli Banovich, Jonathan Andrew Kropski · 2024 to 2026
$2.8M
Haptoglobin 2 variant and endothelial glycocalyx shedding in sepsis-induced ARDSR01HL158906 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WARE, LORRAINE B · 2021 to 2024
$2.3M
Targeting dysfunctional epithelial repair in pulmonary fibrosisR01HL175555 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Timothy S. Blackwell · 2024 to 2026
$1.9M
BLRD VA I01 BX002378Department of Health | National Health and Medical Research Council (NHMRC) GNT1162829Department of Health | National Health and Medical Research Council (NHMRC) GNT1195595NHGRI NIH HHS R01 HG011886NHLBI NIH HHS P01 HL092870NHLBI NIH HHS P01 HL172729NHLBI NIH HHS R01 HL126176NHLBI NIH HHS R01 HL145372NHLBI NIH HHS R01 HL158906NHLBI NIH HHS R01 HL160551NHLBI NIH HHS R01 HL168556NHLBI NIH HHS R01 HL175555NHLBI NIH HHS T32 HL094296NHLBI NIH HHS U01 HL175444United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP) W81XWH1910415U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL126176U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL158906U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) P01HL092870U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL145372U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL160551U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) U01HL175444U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) R01HG011886
6 · The paper itself

Abstract

Large-scale changes in the structure and cellular makeup of the distal lung are a hallmark of pulmonary fibrosis (PF), but the spatial contexts that contribute to disease pathogenesis have remained uncertain. Using image-based spatial transcriptomics, we analyzed the gene expression of 1.6 million cells from 35 unique lungs. Through complementary cell-based and innovative cell-agnostic analyses, we characterized the localization of PF-emergent cell types, established the cellular and molecular basis of classical PF histopathologic features and identified a diversity of distinct molecularly defined spatial niches in control and PF lungs. Using machine learning and trajectory analysis to segment and rank airspaces on a gradient of remodeling severity, we identified compositional and molecular changes associated with progressive distal lung pathology, beginning with alveolar epithelial dysregulation and culminating with changes in macrophage polarization. Together, these results provide a unique, spatially resolved view of PF and establish methods that could be applied to other spatial transcriptomic studies.

Indexed as

Airway RemodelingLungPulmonary FibrosisTranscriptomeAnimalsFemaleGene Expression ProfilingHumansMacrophagesMaleMice

Identifiers

PMID39901013
PMCPMC11906353

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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.