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

Frontiers in Cardiovascular Medicine

Cardiovascular Medicine

Diego A. Lema¹  Taejoon Won¹  Abdel Daoud²  Daniela Čiháková³ 

[1] Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States;W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States;W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States;Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States;

关键词: cardiac sarcoidosis (CS);    pulmonary sarcoidosis;    single-cell RNA-seq (scRNA-seq);    single-nucleus RNA-seq;    meta-analysis;    bioinformactics;   

DOI  :  10.3389/fcvm.2023.1227818

 received in 2023-05-23, accepted in 2023-07-03,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionCardiac 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.MethodsTwo 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.ResultsOur 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.ConclusionsOur 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.

【 授权许可】

Unknown   
© 2023 Daoud, Lema, Won and Čiháková.