瑞典皇家理工学院Patrik L. Ståhl和阿斯利康公司Marianna Stamou等共同合作，近期取得重要工作进展。他们研究绘制了人类和小鼠肺纤维化的空间分辨率转录组图谱。相关研究成果2024年7月1日在线发表于《自然—遗传学》杂志上。

据介绍，特发性肺纤维化（IPF）是一种进展性肺部疾病，预后较差，治疗选择有限。由于对IPF发病机制的了解有限以及现有临床前模型的可转译性差，确定有效治疗方法的努力受到阻碍。

研究人员生成了人IPF（n=4）和博来霉素诱导的小鼠肺纤维化（n=6）的空间分辨转录组图，以解决这些局限性。研究人员在IPF肺中发现了不同的纤维化生态位，其特征是微环境中异常的肺泡上皮细胞，该微环境由转化生长因子β信号和预测的调节因子（如TP53和APOE）主导。研究人员还发现了IPF纤维化生态位中停滞的肺泡再生和急性纤维化小鼠肺中活跃的组织修复之间的明显差异。

总之，这一研究为IPF的转录格局提供了深入的见解，并提出肺泡再生是一种有前景的IPF治疗策略。

附：英文原文

Title: Mapping spatially resolved transcriptomes in human and mouse pulmonary fibrosis

Author: Franzn, Lovisa, Olsson Lindvall, Martina, Hhn, Michael, Ptasinski, Victoria, Setyo, Laura, Keith, Benjamin P., Collin, Astrid, Oag, Steven, Volckaert, Thomas, Borde, Annika, Lundeberg, Joakim, Lindgren, Julia, Belfield, Graham, Jackson, Sonya, Ollerstam, Anna, Stamou, Marianna, Sthl, Patrik L., Hornberg, Jorrit J.

Issue&Volume: 2024-07-01

Abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis and limited treatment options. Efforts to identify effective treatments are thwarted by limited understanding of IPF pathogenesis and poor translatability of available preclinical models. Here we generated spatially resolved transcriptome maps of human IPF (n=4) and bleomycin-induced mouse pulmonary fibrosis (n=6) to address these limitations. We uncovered distinct fibrotic niches in the IPF lung, characterized by aberrant alveolar epithelial cells in a microenvironment dominated by transforming growth factor beta signaling alongside predicted regulators, such as TP53 and APOE. We also identified a clear divergence between the arrested alveolar regeneration in the IPF fibrotic niches and the active tissue repair in the acutely fibrotic mouse lung. Our study offers in-depth insights into the IPF transcriptional landscape and proposes alveolar regeneration as a promising therapeutic strategy for IPF.

DOI: 10.1038/s41588-024-01819-2

Source: https://www.nature.com/articles/s41588-024-01819-2