Plate IV.316 · Publications
Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis
Article in Nature Communications, 16 July 2020.
Abstract
The cell type specific sequences of transcriptional programs during lung regeneration have remained elusive. Using time-series single cell RNA-seq of the bleomycin lung injury model, we resolved transcriptional dynamics for 28 cell types. Trajectory modeling together with lineage tracing revealed that airway and alveolar stem cells converge on a unique Krt8 + transitional stem cell state during alveolar regeneration. These cells have squamous morphology, feature p53 and NFkB activation and display transcriptional features of cellular senescence. The Krt8+ state appears in several independent models of lung injury and persists in human lung fibrosis, creating a distinct cell-cell communication network with mesenchyme and macrophages during repair. We generated a model of gene regulatory programs leading to Krt8+ transitional cells and their terminal differentiation to alveolar type-1 cells. We propose that in lung fibrosis, perturbed molecular checkpoints on the way to terminal differentiation can cause aberrant persistence of regenerative intermediate stem cell states.
Cite
@article{strunz2020alveolar,
title = {{Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis}},
author = {Strunz, Maximilian and Simon, Lukas M. and Ansari, Meshal and Kathiriya, Jaymin J. and Angelidis, Ilias and Mayr, Christoph H. and Tsidiridis, George and Lange, Marius and Mattner, Laura F. and Yee, Min and Ogar, Paulina and Sengupta, Arunima and Kukhtevich, Igor and Schneider, Robert and Zhao, Zhongming and Voss, Carola and Stoeger, Tobias and Neumann, Jens H. L. and Hilgendorff, Anne and Behr, Jürgen and O’Reilly, Michael and Lehmann, Mareike and Burgstaller, Gerald and Königshoff, Melanie and Chapman, Harold A. and Theis, Fabian J. and Schiller, Herbert B.},
journal = {Nature Communications},
publisher = {Springer Science and Business Media LLC},
year = {2020},
month = jul,
doi = {10.1038/s41467-020-17358-3},
url = {https://doi.org/10.1038/s41467-020-17358-3},
pmid = {32678092},
pmcid = {PMC7366678}
}