| First Author | Gacha-Garay MJ | Year | 2025 |
| Journal | bioRxiv | PubMed ID | 40492191 |
| Mgi Jnum | J:391370 | Mgi Id | MGI:8403238 |
| Doi | 10.1101/2025.05.26.654588 | Citation | Gacha-Garay MJ, et al. (2025) Apoptosis inhibition reprograms alveolar myofibroblasts toward ductal myofibroblasts. bioRxiv |
| abstractText | 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. |
