Post by Janine Gote-Schniering

🚨 New preprint alert! 🫁 How does aging derail lung regeneration after injury? We’re excited to share our latest study—now on bioRxiv—offering a high-resolution, time-resolved single-cell atlas of lung repair in young vs. aged mice: 👉 https://lnkd.in/exFpXqNg Proudly co-led with Herbert Schiller and Mareike Lehmann. Aging is the primary risk factor for chronic lung disease, but the cellular and molecular mechanisms preventing proper repair in the aged lung remain poorly understood.  In this study, we combined single cell RNA-seq with functional organoid and PCLS assays to analyze how aging disrupts multicellular gene programs during regeneration after bleomycin-induced fibrosis. We show that lung regeneration in aged mice shifts from a coordinated, transient repair process (as seen in young mice) to a prolonged, maladaptive response that culminates in persistent fibrosis. We observed age-dependent alterations in the emergence and resolution of regenerative cell states (RCSs), and identified a specific epithelial-mesenchymal-immune circuit driving persistent fibrosis in old mice. 🧠 Key insights: - In aged lungs, persistent epithelial-mesenchymal crosstalk and prolonged epithelial senescence are linked to failed fibrosis resolution. - Multicellular gene program analysis revealed that T/B lymphocytes and macrophages are the most affected by aging—challenging the epithelium-centric model of lung fibrosis and emphasizing immune-mediated, multicellular dysregulation. - We identified a unique Granzyme K⁺CD8⁺ T cell population exclusive to aged lungs. These cells localized near alveolar stem cells and, through non-cytotoxic mechanisms, impaired their regenerative capacity by inducing senescence and pro-fibrotic states. 📊 Explore the data yourself—no coding needed! We’ve built an interactive webtool to visualize cell states, gene expression, and intercellular communication: 🔗 https://lnkd.in/ei5swA3S 💡 Developed by Sai Rama Sridatta Prakki Huge thanks to all co-authors who made this work possible! Maria Camila Melo Narvaez, Safwen Kadri, Ph.D, MBA, David Lauer, Meshal Ansari, Matthias Brunner, Huijuan Wang, Yuexin Chen, Ilias Angelidis, PhD, Sara Asgharpour, Gowtham Boosarpu, Eshita Jain, Simrah Khan, Christoph Mayr, Michael Dudek, Gerald Burgstaller, Percy A. Knolle, Oender Yildirim, Melanie Königshoff, Fabian Theis