TY - JOUR T1 - A smooth muscle-like niche facilitates lung epithelial regeneration JF - bioRxiv DO - 10.1101/565085 SP - 565085 AU - Alena Moiseenko AU - Ana Ivonne Vazquez-Armendariz AU - Xuran Chu AU - Stefan Günther AU - Kevin Lebrigand AU - Vahid Kheirollahi AU - Susanne Herold AU - Thomas Braun AU - Bernard Mari AU - Stijn De Langhe AU - Chengshui Chen AU - Xiaokun Li AU - Werner Seeger AU - Jin-San Zhang AU - Saverio Bellusci AU - Elie El Agha Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/03/01/565085.abstract N2 - 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 combining in vivo lineage tracing, single-cell RNA sequencing and in vitro organoid 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. ER -