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Cited by 4,984Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisSingle-cell and spatial transcriptomicsTransplantation: Methods and Outcomes

Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage

Open access
Aran, Dvir, Looney, Agnieszka P., Liu, Leqian, Wu, Esther, Fong, Valerie, Hsu, Austin, Chak, Suzanna, Naikawadi, Ram P. +4 more·2019·Nature Immunology
DOI 10.1038/s41590-018-0276-yPMC PMC6340744

Published version of a preprint

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Abstract

Tissue fibrosis is a major cause of mortality that results from the deposition of matrix proteins by an activated mesenchyme. Macrophages accumulate in fibrosis, but the role of specific subgroups in supporting fibrogenesis has not been investigated in vivo. Here, we used single-cell RNA sequencing (scRNA-seq) to characterize the heterogeneity of macrophages in bleomycin-induced lung fibrosis in mice. A novel computational framework for the annotation of scRNA-seq by reference to bulk transcriptomes (SingleR) enabled the subclustering of macrophages and revealed a disease-associated subgroup with a transitional gene expression profile intermediate between monocyte-derived and alveolar macrophages. These CX3CR1+SiglecF+ transitional macrophages localized to the fibrotic niche and had a profibrotic effect in vivo. Human orthologs of genes expressed by the transitional macrophages were upregulated in samples from patients with idiopathic pulmonary fibrosis. Thus, we have identified a pathological subgroup of transitional macrophages that are required for the fibrotic response to injury. Using scRNA-seq analysis, Bhattacharya and colleagues identify a subset of profibrotic lung macrophages that have a gene expression signature intermediate between those of monocytes and alveolar macrophages.

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Crossref · 10.1038/s41590-018-0276-y

Cites

59 of 59 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 26 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Expression of these genes in SiglecF+CD11c+MHCIIhi cells at 4 weeks after injury was reduced to levels more similar to steady-state alveolar macrophages.

    “the expression of these genes in SiglecF+CD11c+MHCIIhi cells at 4 weeks after injury was reduced to levels more similar to those detected in SiglecF+CD11c+ alveolar macrophages at steady-state”
    Quote in the paperSubstantial claim
  • Findingown data

    MAFB, a marker detected specifically in clusters C2 and C3, was expressed in CD68+ macrophages from patients with idiopathic lung fibrosis compared to healthy controls.

    “immunofluorescence of lung tissue indicated the expression of MAFB, a marker detected specifically in clusters C2 and C3, in CD68+ macrophages from patients with idiopathic lung fibrosis compared to healthy controls”
    Quote in the paperSubstantial claim
  • Findingown data

    The SingleR annotation scores for alveolar and interstitial macrophages were strongest at the poles of the macrophage cluster.

    “The annotation scores for alveolar and interstitial macrophages were strongest at the poles of the macrophage cluster”
    Quote in the paperSubstantial claim
  • Findingown data

    The lung scRNA-seq dataset annotated by SingleR showed three clusters of fibroblasts, A, B and C.

    “showed three clusters of fibroblasts, cluster A, B, and C”
    Quote in the paperNot a substantial claim
  • Findingown data

    TdTomato-SiglecF+ alveolar macrophages were detectable throughout the lung except in regions where Pdgfrb+ fibroblasts accumulated at injury sites.

    “TdTomato-SiglecF+ alveolar macrophages (cluster C1) were detectable throughout the lung except in regions where Pdgfrb+ fibroblasts accumulated at sites of injury”
    Quote in the paperSubstantial claim
  • May combine two claims. 19
  • Classified as probably not a substantial claim. 14
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data

    C1 had higher expression of alveolar macrophage genes than C2, which in turn had higher alveolar macrophage genes than C3.

    “C1 had higher expression of alveolar macrophage genes than cluster C2, which in turn had higher alveolar macrophage genes than cluster C3”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Clusters C2 and C3 were enriched in cells from bleomycin-induced fibrosis and expressed Cx3cr1, Ccr2, Mafb and MHCII genes, consistent with monocytic origin.

    “Clusters C2 and C3 were enriched in cells isolated from mice with bleomycin-induced fibrosis and expressed Cx3cr1, Ccr2, Mafb and MHCII genes, consistent with monocytic origin”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Cluster A showed the highest expression of cell cycle genes and was predominantly composed of cells from bleomycin-treated mice.

    “Cluster A showed the highest expression of cell cycle genes and was predominantly composed of cells from bleomycin-treated mice”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    SingleR is a computational method that assigns cell identity to single-cell transcriptomes by correlating them with reference bulk RNA-seq or microarray datasets of pure cell types and iteratively improving its inferences.

    “We developed a computational tool for unbiased annotation as well as clustering of scRNA-seq, called SingleR (single cell recognition). SingleR assigns cellular identity for single cell transcriptomes by comparison to reference datasets of pure cell types sequenced by microarray or RNA-seq.”
    • Also stated in: § Reference datasets enhance annotation of scRNA-seq · plain
      “we developed a computational method called SingleR, which correlated single cell transcriptomes with reference transcriptomic datasets and improved its inferences iteratively”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Hierarchical clustering of SingleR correlation scores identified three distinct macrophage subclusters, C1, C2 and C3, all detected at varying levels in both steady-state and bleomycin-treated mice.

    “This analysis identified three distinct subclusters (C1, C2 and C3), all three detected at varying levels in both steady-state and bleomycin-treated mice”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Cluster C1 was equally present in steady-state lung and bleomycin injury and corresponded to cells annotated as alveolar macrophages by lung-specific datasets.

    “cluster C1 was equally present in steady-state lung and bleomycin injury and corresponded to the cells that were annotated as alveolar macrophages by the lung-specific datasets”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    45% of cluster C2 cells, but only 7.3% of cluster C1 cells and 4.7% of cluster C3 cells, expressed at least 33% of cluster C1 genes and at least 33% of cluster C3 genes.

    “45% of cluster C2 cells (but only 7.3% of cluster C1 cells and 4.7% of cluster C3 cells) expressed at least 33% of cluster C1 genes and at least 33% of cluster C3 genes”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingreasoning

    Pdgfra was not detected in the lung scRNA-seq dataset, which may reflect limited sequencing depth.

    “Pdgfra was not detected in the lung scRNA-seq dataset, which may reflect the limitation of the depth of sequencing with the single-cell method”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In human lung fibrosis samples, expression of genes associated with alveolar macrophages (cluster C1) was significantly decreased and expression of MHC II genes (clusters C2 and C3) was significantly increased compared to healthy controls.

    “This analysis showed a significant decrease in the expression of genes associated with alveolar macrophages (cluster C1) and a significant increase in the expression of MHC II genes (cluster C2 and C3) in the human fibrosis samples compared to the healthy controls”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] Naikawadi, R. P. et al. Telomere dysfunction in alveolar epithelial cells causes lung remodeling and fibrosis. JCI Insight 1, e86704 (2016). source

      Not checked in the free run.

    • Rests on an assumption: Changes in expression of human orthologues in bulk lung microarray samples reflect changes in macrophage populations rather than other cell types.

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    At 21 days after bleomycin injury, tamoxifen-induced Cx3cr1-CreERT2/Rosa26-DTA mice had significantly fewer macrophages, significantly decreased Pdgfra+ and Pdgfrb+ cells, and significantly decreased lung collagen by hydroxyproline compared to bleomycin-injured wild-type mice.

    “At 21 days after bleomycin injury, bleomycin-injured, tamoxifen-induced Cx3cr1-CreERT2 / Rosa26-loxp-STOP-loxp-Diphteria Toxin A mice had significantly fewer macrophages quantified by immunofluorescent labeling of either Mertk+ or SiglecF+ cells in the lung”
    • Also stated in: § Discussion · plain
      “Deletion of these macrophages during the fibrotic period (days 8–21) eliminated Pdgfra+ or Pdgfrb+ fibroblasts and total lung collagen.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The filtered single-cell RNA-seq dataset contained 8,366 cells and 13,861 genes.

    “Altogether, the filtered data contained 8,366 cells and 13,861 genes (Supplementary Table 1).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A significant expansion of Pdgfra+ fibroblasts after bleomycin treatment has been reported in a study analyzing the fibroblast compartment in this fibrosis model.

    “a significant expansion of Pdgfra+ fibroblasts after bleomycin treatment has been reported in a study analyzing the fibroblast compartment in this model of fibrosis 35”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Yona, S. et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38, 79–91 (2013). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The telomere dysfunction model results are consistent with a common genetic signature and a generalizable pattern of macrophage response during fibrogenesis.

    “the results are consistent with a common genetic signature and a generalizable pattern of macrophage response during fibrogenesis”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The results demonstrate the value of reference-based annotation of single-cell datasets for mapping heterogeneity of canonical cell types and enhancing differentiation of transcriptomically unique subclusters.

    “Our results also demonstrate the value of using reference-based annotation of single cell datasets in order to map the heterogeneity of canonical cell types, such as macrophages, and to enhance the differentiation of transcriptomically unique subclusters within the data.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    SingleR uses the 80th percentile of correlation values to prevent misclassification due to heterogeneity in the reference samples.

    “SingleR uses the 80th percentile of correlation values, to prevent misclassification due to heterogeneity in the reference samples.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All animal experiments were approved by the UCSF Institutional Animal Care and Use Committee.

    “All animal experiments were in accordance with protocols approved by the UCSF Institutional Animal Care and Use Committee.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Annotation of cell states using SingleR relies on the particularities of the reference datasets.

    “our annotation of cell states using SingleR relies on the particularities of the reference datasets”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Written informed consent was obtained from all human subjects, and the study was approved by the UCSF institutional review board.

    “Written informed consent was obtained from all subjects, and the study was approved by the UCSF institutional review board.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The analysis suggests an evolution of cluster C3 toward cluster C1, with C2 representing a transitional state.

    “Our analysis suggests an evolution of cluster C3 towards cluster C1, with C2 representing a transitional state.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisereasoning

    The ImmGen database is a large compendium of cell types from multiple organs, which facilitated the clustering analysis by differential annotation.

    “The ImmGen database is a large compendium of cell types from multiple organs, which greatly facilitated our clustering analysis by differential annotation.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Heng, T. S. & Painter, M. W. The Immunological Genome Project Consortium. The Immunological Genome Project: networks of gene expression in immune cells. Nat. Immunol. 9, 1091–1094 (2008). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Yang et al. performed gene expression profiling for 167 lung tissues from idiopathic interstitial pneumonia subjects and 50 healthy controls.

    “Yang et al.32 performed gene expression profiling for 167 lung tissues from idiopathic interstitial pneumonia subjects and 50 healthy controls.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Yang et al.32

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Study design and conductnone given

    The control lungs used in the study are physiologically and pathologically normal.

    “Our studies indicate that these lungs are physiologically and pathologically normal.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Paracrine interactions between these macrophages and fibroblasts sustain fibroblast proliferation and tissue fibrosis.

    “suggesting that paracrine interactions between these macrophages and fibroblasts sustain fibroblast proliferation and tissue fibrosis”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    These findings underscore the potential therapeutic significance of the functional studies in mice.

    “These findings underscore the potential therapeutic significance of our functional studies in mice.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The bleomycin-induced mouse lung fibrosis model recapitulates key features of human lung fibrosis, so findings in it can inform human disease.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given

    Strain-appropriate controls were used in all experiments.

    “Strain-appropriate controls were used in all experiments”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given

    Using only variable genes increases the ability to distinguish closely related cell types.

    “Using only variable genes increases the ability to distinguish closely related cell types.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All Agilent microarray samples passed the quality control parameters established by Agilent.

    “All the samples passed the quality control parameters established by Agilent.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    This study identified a profibrotic macrophage subpopulation that localizes to sites of fibrotic scar and has activating effects on the mesenchyme.

    “this study identified a profibrotic macrophage subpopulation that localizes to sites of fibrotic scar with activating effects on the mesenchyme”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Fibroblast migration and proliferation were dependent on secretion of Pdgf-aa by SiglecF+CD11c+MHCIIhi and CX3CR1+ cells, respectively.

    “Mechanistic studies indicated that fibroblast migration and proliferation were dependent on secretion of Pdgf-aa by SiglecF+CD11c+MHCIIhi and CX3CR1+ cells, respectively”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 3T3 embryonic mouse fibroblast cell line is a valid proxy for lung fibroblasts in fibrosis for assessing migration and proliferation.
    • Rests on an assumption: The Pdgf-aa blocking antibody specifically neutralizes Pdgf-aa without affecting other PDGF isoforms or unrelated pathways.
29 of 29

  • The paper relies on this without support.

    The bleomycin-induced mouse lung fibrosis model recapitulates key features of human lung fibrosis, so findings in it can inform human disease.

    “Our observation that ablation of macrophages expressing Cx3cr1 decreased fibroblasts and lung collagen content after bleomycin treatment has relevance for human disease.”

  • The paper relies on this without support.

    The 3T3 embryonic mouse fibroblast cell line is a valid proxy for lung fibroblasts in fibrosis for assessing migration and proliferation.

    “we performed in vitro assays with 3T3 fibroblasts, an embryonic mouse fibroblast cell line.”

  • The paper relies on this without support.

    The Pdgf-aa blocking antibody specifically neutralizes Pdgf-aa without affecting other PDGF isoforms or unrelated pathways.

    “Antibody blockade of Pdgf-aa inhibited the enhanced gap closure seen in SiglecF+CD11c+MHCIIhi compared to SiglecF+CD11c+MHCIIlo conditioned media”

  • The paper relies on this without support.

    Changes in expression of human orthologues in bulk lung microarray samples reflect changes in macrophage populations rather than other cell types.

    “we performed single-sample gene set enrichment analysis (ssGSEA)31 to quantify the expression of human orthologues of genes of interest in a published microarray dataset of 167 lung samples from patients with lung fibrosis and 50 healthy controls32”

  • The paper relies on this without support.

    The human lung explants with regional heterogeneity are representative of idiopathic pulmonary fibrosis fibrotic foci.

    “In three lung explants displaying such regional heterogeneity, we found that PDGF-AA+ macrophages were associated with the fibrotic rather than non-fibrotic regions”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The pathogenic role of Mo-AMs in lung fibrosis is largely attributed to their production of pro-fibrotic mediators such as TGF-β, PDGF-α, osteopontin, and MMPs.

    “The pathogenic role of Mo-AMs in lung fibrosis has been largely attributed to their activity in producing a number of pro-fibrotic mediators, such as TGF-β, PDGF-α, osteopontin (OPN), and MMPs1,3,11,13,15,18,28.”

    From TREM2 promotes lung fibrosis via controlling alveolar macrophage survival and pro-fibrotic activity (2025) · cites this paper as [18]

    The Results (‘CX3CR1-expressing macrophages drive lung fibrosis’) and Discussion identify profibrotic macrophages as a source of PDGF-AA and link it to fibroblast proliferation. The passages support that mediator, but do not establish macrophage production of TGF-β, osteopontin, or MMPs as the basis of their pathogenic role. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • M3-TAMs (FABP4+ TAMs) are dominant in the lung metastatic osteosarcoma lesion.

    “the M3-TAMs, actually the FABP4+ TAMs previously identified as the alveolar macrophages in the lung, were dominant in the lung metastatic osteosarcoma lesion [24].”

    From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [24]

    The Discussion identifies a lung alveolar macrophage cluster (C1), supporting only the sentence’s reference to previously identified alveolar macrophages. The Results section on the fibrotic niche studies lung fibrosis, not osteosarcoma metastases; our copy does not establish that FABP4+ M3-TAMs are alveolar macrophages or dominant in a metastatic lesion (searched: FABP4, osteosarcoma, metastasis). Page numbers were not available in the indexed passages. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Myeloid clusters were identified by checking canonical myeloid marker gene expression and by automated annotation with SingleR based on the Novershtern immune reference dataset.

    “To identify myeloid clusters, we checked the expression of canonical myeloid marker genes (Supplementary Data 3). Furthermore, we used SingleR v2.0.074 for automated annotation based on the Novershtern immune reference dataset75 from the celldex v1.8.0 package74.”

    From CHIT1 at diagnosis predicts faster disability progression and reflects early microglial activation in multiple sclerosis (2024) · cites this paper as [74]

    The Results section ('Reference datasets enhance annotation of scRNA-seq') identifies SingleR as a method for automated cell-type annotation using reference transcriptomes, supporting its use for that purpose. The cited paper does not identify SingleR v2.0.0 or the celldex v1.8.0 package, both of which carry this citation in the citing sentence. The Novershtern dataset has a separate citation, and checking marker genes is described as the citing authors’ own step. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • SoupX version 1.5.2 was used to identify and remove ambient RNA background noise from the scRNA-seq data.

    “To address the ambient RNA contamination SoupX version 1.5.2[54] was utilized to identify and remove ambient RNA background noise from the data.”

    From Single-cell transcriptomics unveils skin cell specific antifungal immune responses and IL-1Ra- IL-1R immune evasion strategies of emerging fungal pathogen Candida auris (2024) · cites this paper as [54]

    The Results section describes SingleR for cell-type annotation, while Online Methods (Drop-seq and data analysis; page unavailable) describes processing and clustering with Seurat. Searches for SoupX, version 1.5.2, and ambient RNA correction found no passage addressing the claimed use of SoupX. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

  • The pericellular fibrotic matrix is a remarkably dynamic environment that exerts profound influences on cell behavior, and many key cell-cell and cell-matrix interactions that regulate fibrosis are mediated by members of the integrin family.

    “The pericellular fibrotic matrix is a remarkably dynamic environment, which exerts profound influences on cell behavior, and many of the key cell–cell and cell–matrix interactions which regulate fibrosis are mediated by members of the integrin family (noncovalent α/β heterodimers from 18 different α subunits and 8 β subunits resulting in 24 known members in humans)86,87.”

    From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [86]

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Authors
Aran, D., Looney, A. P., Liu, L., Wu, E., Fong, V., Hsu, A., Chak, S., Naikawadi, R. P., Wolters, P. J., Abate, A. R., Butte, A. J., & Bhattacharya, M.
Affiliations
  • University of California, San Francisco (US)
  • Gladstone Institutes (US)
  • QB3 (US)
Corresponding author
Bhattacharya, Mallar
ORCID
Venue
Nature Immunology
Publisher
Springer Science and Business Media LLC
Published
2019-01-14
Volume
20
Issue
2
Pages
163-172
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
DOI
10.1038/s41590-018-0276-y
PMC
PMC6340744
OpenAlex
W2907514116
Semantic Scholar
a4d99547655d02c1cfa5d8c627a10248507b96f2
Cited by
4,984
References
56
Citations by year
2026: 831 · 2025: 1024 · 2024: 966 · 2023: 856 · 2022: 662 · 2021: 394 · 2020: 181 · 2019: 63 · 2018: 3
FWCI
249.29
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Immunology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Gladstone Institutes
  • National Institutes of Health (HHSN272201200028C)
  • University of California, San Francisco
  • National Heart, Lung, and Blood Institute (L30 HL110167, R01HL131560, R01HL139897)
  • National Institute of Allergy and Infectious Diseases (HHSN272201200028C)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
Keywords
pulmonary fibrosis, macrophage heterogeneity, bleomycin-induced lung fibrosis, idiopathic pulmonary fibrosis, monocyte-derived macrophages, alveolar macrophages, CX3CR1, fibrotic niche, macrophage activation
MeSH terms
CX3C Chemokine Receptor 1, Animals, Bleomycin, Cells, Cultured, Disease Models, Animal, Female, Humans, Lung, Macrophage Activation, Male, Antigens, Differentiation, Myelomonocytic, Up-Regulation, Macrophages, Alveolar, Sequence Analysis, RNA, Gene Expression Profiling, Mice, Idiopathic Pulmonary Fibrosis, Single-Cell Analysis, Sialic Acid Binding Immunoglobulin-like Lectins

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