Boehringer Ingelheim Pharma GmbH & Co. KG, Department Immunology and Respiratory Disease research, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany.
Boehringer Ingelheim Pharma GmbH & Co. KG, Global Computational Biology and Digital Sciences, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany.
Sci Adv. 2024 Aug 9;10(32):eadl5473. doi: 10.1126/sciadv.adl5473.
Despite advancements in antifibrotic therapy, idiopathic pulmonary fibrosis (IPF) remains a medical condition with unmet needs. Single-cell RNA sequencing (scRNA-seq) has enhanced our understanding of IPF but lacks the cellular tissue context and gene expression localization that spatial transcriptomics provides. To bridge this gap, we profiled IPF and control patient lung tissue using spatial transcriptomics, integrating the data with an IPF scRNA-seq atlas. We identified three disease-associated niches with unique cellular compositions and localizations. These include a fibrotic niche, consisting of myofibroblasts and aberrant basaloid cells, located around airways and adjacent to an airway macrophage niche in the lumen, containing SPP1 macrophages. In addition, we identified an immune niche, characterized by distinct lymphoid cell foci in fibrotic tissue, surrounded by remodeled endothelial vessels. This spatial characterization of IPF niches will facilitate the identification of drug targets that disrupt disease-driving niches and aid in the development of disease relevant in vitro models.
尽管抗纤维化疗法取得了进展,但特发性肺纤维化(IPF)仍然是一种存在未满足需求的医学病症。单细胞 RNA 测序(scRNA-seq)增强了我们对 IPF 的理解,但缺乏空间转录组学提供的细胞组织背景和基因表达定位。为了弥补这一差距,我们使用空间转录组学对 IPF 和对照患者的肺组织进行了分析,将这些数据与 IPF 的 scRNA-seq 图谱进行了整合。我们确定了三个与疾病相关的生态位,它们具有独特的细胞组成和定位。其中包括一个纤维化生态位,由肌成纤维细胞和异常的基底样细胞组成,位于气道周围,与气道腔中的气道巨噬细胞生态位相邻,其中含有 SPP1 巨噬细胞。此外,我们还确定了一个免疫生态位,其特征是纤维化组织中存在独特的淋巴样细胞灶,周围是重塑的内皮血管。这些 IPF 生态位的空间特征将有助于确定破坏疾病驱动生态位的药物靶点,并有助于开发与疾病相关的体外模型。
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