Daoud Abdel, Lema Diego A, Won Taejoon, Čiháková Daniela
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.
Front Cardiovasc Med. 2023 Jul 28;10:1227818. doi: 10.3389/fcvm.2023.1227818. eCollection 2023.
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.
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.
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.
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.
自身免疫性结节病的心脏表现，即心脏结节病（CS），是一种了解甚少的疾病，死亡率高且诊断率低。虽然CS是一种免疫综合征，但对于心脏实质细胞和基质细胞如何介导其发病机制知之甚少。此外，虽然目前大多数结节病研究基于肺结节病（PS）的研究，但尚不清楚这两种结节病表现形式的重叠程度。为了解决这些问题，我们利用了公开可用的结节病转录组数据集。
整合两个公开可用的支气管肺泡灌洗单细胞RNA测序数据集，以分析PS与对照相比的情况。此外，整合两个公开可用的心脏单核RNA测序数据集，以分析CS与对照相比的情况。整合后，我们对分析中确定的实质、基质和免疫亚群进行了细胞间通讯、转录因子和差异表达分析。
我们的分析表明，PS和CS中基质细胞和免疫细胞有所扩增。我们还观察到，与对照相比，CS和PS免疫细胞中Th17.1上调，激活转录谱减弱。此外，我们发现，与对照相比，CS心脏基质细胞中促炎和促纤维化转录谱上调。我们还发现，与对照相比，CS中心肌细胞的心脏应激和增殖转录谱上调。
我们的综合转录组分析表明，尽管存在组织特异性差异，但CS和PS之间存在共同的转录趋势。它还表明，基质和实质群体呈现出可以解释它们在CS中致病作用的转录趋势。
