Work

Apoptosis inhibition reprograms alveolar myofibroblasts toward ductal myofibroblasts

Year: 2026

Type: article

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-seq, 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 the apoptotic clearance of AMFs, as well as fate plasticity and pathophysiological convergence of lung mesenchymal cells of the epithelial axis.

Source: Cell Reports

DOI: 10.1016/j.celrep.2026.117891

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

Institutions: The University of Texas MD Anderson Cancer Center, The University of Texas Health Science Center at Houston, Cincinnati Children's Hospital Medical Center, University of Cincinnati

Language: English

Topic: Asthma and respiratory diseases

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,620