| First Author | Gacha-Garay MJ | Year | 2026 |
| Journal | Cell Rep | Volume | 45 |
| Issue | 9 | Pages | 117891 |
| PubMed ID | 42704712 | Mgi Jnum | J:392022 |
| Mgi Id | MGI:8408740 | Doi | 10.1016/j.celrep.2026.117891 |
| Citation | Gacha-Garay MJ, et al. (2026) Apoptosis inhibition reprograms alveolar myofibroblasts toward ductal myofibroblasts. Cell Rep 45(9):117891 |
| 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 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. |
