Apoptosis inhibition reprograms alveolar myofibroblasts toward ductal myofibroblasts.

Authors

Maria Jose Gacha-Garay, Hui Liu, Scott E Evans, Tingting W Mills, Jichao Chen

Published in

Cell reports. Volume 45. Issue 9. Pages 117891. Sep 07, 2026. Epub Sep 07, 2026.

Abstract

The epithelial tree of the lung is shaped proximo-distally by airway smooth muscle cells (ASMCs), ductal myofibroblasts (DMFs), and, transiently, alveolar myofibroblasts (AMFs). Lineage tracing and snapshot imaging suggest the clearance of AMFs via apoptosis post-alveologenesis, although definitive evidence is lacking. Here, we generate an inducible BCL2 overexpression mouse allele to inhibit AMF apoptosis. Using three independent Cre drivers and single-cell RNA sequencing, we show that BCL2-rescued AMFs persist around distal alveolar ducts and alveoli and, unexpectedly, mature toward DMFs. Both normal DMFs and rescued DMF-like cells upregulate contractile proteins in a house dust mite-induced asthma model. Our findings demonstrate apoptosis as the chief mechanism of AMF clearance, as well as fate plasticity and pathophysiological convergence of lung mesenchymal cells of the epithelial axis.

PMID:
42704712
Bibliographic data and abstract were imported from PubMed on 08 Sep 2026.

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