A smooth muscle-like niche facilitates lung epithelial regeneration

Autor: Alena Moiseenko, Xuran Chu, Bernard Mari, Susanne Herold, Stefan Guenther, Ana Ivonne Vazquez-Armendariz, S De Langhe, Xianfeng Li, Kevin Lebrigand, Chao Chen, Werner Seeger, Thomas Braun, Elie El Agha, Saverio Bellusci, Vahid Kheirollahi, Jin-San Zhang
Rok vydání: 2019
Předmět:
Popis: The mammalian lung is a highly complex organ due to its branched, tree-like structure and diverse cellular composition. Recent efforts using state-of-the-art genetic lineage tracing and single-cell transcriptomics have helped reduce this complexity and delineate the ancestry and fate of various cell subpopulations during organogenesis, homeostasis and repair after injury. However, mesenchymal cell heterogeneity and function in development and disease remain a longstanding issue in the lung field. In this study, we break down smooth muscle heterogeneity into the constituent subpopulations by combiningin vivolineage tracing, single-cell RNA sequencing andin vitroorganoid cultures. We identify a repair-supportive mesenchymal cell (RSMC) population that is distinct from pre-existing airway smooth muscle cells (ASMC) and is critical for regenerating the conducting airway epithelium. Progenitors of RSMCs are intertwined with airway smooth muscle, undergo active WNT signaling, transiently acquire the expression of the smooth muscle marker ACTA2 in response to epithelial injury and are marked by PDGFRα expression. Our data simplify the cellular complexity of the peribronchiolar domain of the adult lung and represent a forward step towards unraveling the role of mesenchymal cell subpopulations in instructing epithelial behavior during repair processes.
Databáze: OpenAIRE