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Cited by 10Sarcoidosis and Beryllium Toxicity ResearchAtherosclerosis and Cardiovascular DiseasesSingle-cell and spatial transcriptomics

Integrative single-cell analysis of cardiac and pulmonary sarcoidosis using publicly available cardiac and bronchoalveolar lavage fluid sequencing datasets

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Daoud, Abdel, Lema, Diego A., Won, Taejoon, Čiháková, Daniela·2023·Frontiers in Cardiovascular Medicine
DOI 10.3389/fcvm.2023.1227818PMC PMC10419306
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Abstract

Introduction: Cardiac presentation of autoimmune sarcoidosis, known as cardiac sarcoidosis (CS), is a poorly understood disease with high mortality and low diagnosis rate. While CS is an immunological syndrome, little is known about how cardiac parenchymal and stromal cells mediate its pathogenesis. Moreover, while most current sarcoidosis research is based on research in pulmonary sarcoidosis (PS), it remains unclear how much both presentations of sarcoidosis overlap. To tackle these concerns, we leveraged publicly available sarcoidosis transcriptomic datasets. Methods: Two publicly available bronchoalveolar lavage single-cell RNA sequencing datasets were integrated to analyze PS relative to control. Additionally, two publicly available cardiac single-nucleus RNA sequencing datasets were integrated to analyze CS relative to control. Following integration, we ran cell-cell communication, transcription factor, and differential expression analyses on parenchymal, stromal, and immune subsets identified in our analysis. Results: Our analysis revealed that there was an expansion of stromal and immune cells in PS and CS. We also observed upregulation of Th17.1 and attenuated activation transcriptional profiles in the immune cells of CS and PS relative to control. Additionally, we found upregulation of pro-inflammatory and pro-fibrotic transcriptional profiles in the cardiac stromal cells of CS relative to control. We also found that cardiomyocytes exhibited upregulated cardiac stress and proliferation transcriptional profiles in CS relative to control. Conclusions: Our integrative transcriptomic analysis shows that despite tissue-specific differences, there are shared transcriptional trends between CS and PS. It also shows that stromal and parenchymal populations exhibit transcriptional trends that could explain their pathogenic role in CS.

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  • These macrophages have upregulated mTOR signaling and alternative activation pathway and downregulated cytokine signaling and phagocytosis functions.

    “with upregulated mTOR (mammalian target of rapamycin) signaling and alternative activation pathway as well as downregulated cytokine signaling and phagocytosis functions.”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [217]

    The Results section on sarcoidotic cardiac and BAL macrophages reports upregulated alternative-activation pathways and downregulated cytokine signaling and phagocytosis relative to controls. It reports enrichment of mTOR-related transcription factors, but does not establish upregulated mTOR signaling in both macrophage populations; the Discussion describes upregulated mTOR signaling in cardiac sarcoidosis as the focus of an earlier study. No page numbers are available in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Distinct macrophage subsets from different origins contribute to sarcoidotic granuloma formation in the heart.

    “distinct macrophage subsets from different origins contribute to sarcoidotic granuloma formation in the heart”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [217]

    The Results section ('Sarcoidotic cardiac and BAL MΦ exhibit attenuated alternative activation'; page unavailable) identifies distinct cardiac macrophage subgroups. The Discussion (page unavailable) calls macrophages core constituents of sarcoidotic granulomas, but says their pathogenic role remains unclear. It does not establish that the subgroups have different origins or that they contribute to granuloma formation in the heart. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • T cells, particularly IFNγ-producing Th17 cells, are a key immunologic feature in sarcoidosis.

    “studies indicate the involvement of T cells, particularly IFNγ -producing Th17 cells, as a key immunologic feature in sarcoidosis.”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [217]

  • In cardiac sarcoidosis, nonhematopoietic resident heart cells show a dysregulated transcription program including profibrotic proinflammatory fibroblasts, fibroblast-like angiogenic endothelial cells, and proinflammatory stress-related cardiomyocytes.

    “a dysregulated transcription program in nonhematopoietic resident heart cells under conditions of cardiac sarcoidosis including profibrotic, proinflammatory fibroblasts; fibroblast-like, angiogenic endothelial cells; and proinflammatory, stressrelated cardiomyocytes.”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [217]

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Cited by

Sorted by citations

Authors
Daoud, A., Lema, D. A., Won, T., & Čiháková, D.
Affiliations
Johns Hopkins University (US)
Corresponding author
Čiháková, Daniela
ORCID
Venue
Frontiers in Cardiovascular Medicine
Publisher
Frontiers Media SA
Published
2023-07-28
Volume
10
Pages
1227818-1227818
ISSN
2297-055X (ISSN-L)
DOI
10.3389/fcvm.2023.1227818
PMC
PMC10419306
OpenAlex
W4385334857
Cited by
10
References
2
Citations by year
2026: 5 · 2025: 3 · 2024: 2
FWCI
0.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Cardiovascular Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • American Heart Association (23EIA1040103, 19TPA34910007, 20TPA35490421)
  • National Institutes of Health (19TPA34910007)
  • National Heart, Lung, and Blood Institute (R01HL136586, 19TPA34910007, R01HL118183)
Topics
  • Health Sciences › Medicine › Physiology › Sarcoidosis and Beryllium Toxicity Research
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
Keywords
cardiac sarcoidosis, pulmonary sarcoidosis, single-cell RNA sequencing, single-nucleus RNA sequencing, bronchoalveolar lavage, cardiac stromal cells, Th17 cells, intercellular communication, transcription factors, cardiomyocytes, myocardial fibrosis, pathogenesis

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