Academic Journal
Apoptosis inhibition reprograms alveolar myofibroblasts toward ductal myofibroblasts.
| Title: | Apoptosis inhibition reprograms alveolar myofibroblasts toward ductal myofibroblasts. |
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| Authors: | Gacha-Garay MJ; Department of Pulmonary Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA., Liu H; Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Evans SE; Department of Pulmonary Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Mills TW; Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Electronic address: tingting.weng@uth.tmc.edu., Chen J; Department of Pulmonary Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Pediatrics, Perinatal Institute Division of Pulmonary Biology, University of Cincinnati and Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Electronic address: jichao.chen@cchmc.org. |
| Source: | Cell reports [Cell Rep] 2026 Sep 22; Vol. 45 (9), pp. 117891. Date of Electronic Publication: 2026 Sep 07. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
| MeSH Terms: | Myofibroblasts*/metabolism , Myofibroblasts*/cytology , Pulmonary Alveoli*/metabolism , Pulmonary Alveoli*/cytology , Apoptosis* , Cellular Reprogramming*, Proto-Oncogene Proteins c-bcl-2/metabolism ; Proto-Oncogene Proteins c-bcl-2/genetics ; Animals ; Mice ; Lung |
| 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. (Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of interests The authors declare no competing interests. |
| Comments: | Update of: bioRxiv. 2025 May 28:2025.05.26.654588. doi: 10.1101/2025.05.26.654588.. (PMID: 40492191) |
| Grant Information: | R01 AR073284 United States AR NIAMS NIH HHS; R01 HL168128 United States HL NHLBI NIH HHS |
| Contributed Indexing: | Keywords: CP: developmental biology; alveolar myofibroblast; alveologenesis; apoptosis; cell fate plasticity and reprogramming; lung development |
| Substance Nomenclature: | 0 (Proto-Oncogene Proteins c-bcl-2) |
| Entry Date(s): | Date Created: 20260907 Date Completed: 20260924 Latest Revision: 20260924 |
| Update Code: | 20260924 |
| DOI: | 10.1016/j.celrep.2026.117891 |
| PMID: | 42704712 |
| Database: | MEDLINE |
| ISSN: | 2211-1247 |
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| DOI: | 10.1016/j.celrep.2026.117891 |