Bronchioalveolar Stem Cells Are a Main Source for Regeneration of Distal Lung Epithelia

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2019 Apr 28

PMID 31028085

Citations 89

Authors

Isabelle Salwig

Birgit Spitznagel

Ana Ivonne Vazquez-Armendariz

Keynoosh Khalooghi

Stefan Guenther

Susanne Herold

Marten Szibor

Thomas Braun

Affiliations

Soon will be listed here.

Abstract

Bronchioalveolar stem cells (BASCs) are a potential source for lung regeneration, but direct evidence for a multipotential lineage contribution during homeostasis and disease is critically missing, since specific genetic labeling of BASCs has not been possible. We developed a novel cell tracing approach based on intein-mediated assembly of newly engineered split-effectors, allowing selective targeting of dual-marker expressing BASCs in the mouse lung. RNA sequencing of isolated BASCs demonstrates that BASCs show a distinct transcriptional profile, characterized by co-expression of bronchiolar and alveolar epithelial genes. We found that BASCs generate the majority of distal lung airway cells after bronchiolar damage but only moderately contribute to cellular turnover under homeostatic conditions. Importantly, DTA-mediated ablation of BASCs compromised proper regeneration of distal airways. The study defines BASCs as crucial components of the lung repair machinery and provides a paradigmatic example for the detection and manipulation of stem cells that cannot be recognized by a single marker alone.

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