Details

Autor(en) / Beteiligte

• Strunz, Maximilian
• Simon, Lukas M
• Ansari, Meshal
• Kathiriya, Jaymin J
• Angelidis, Ilias
• Mayr, Christoph H
• Tsidiridis, George
• Lange, Marius
• Mattner, Laura F
• Yee, Min
• Ogar, Paulina
• Sengupta, Arunima
• Kukhtevich, Igor
• Schneider, Robert
• Zhao, Zhongming
• Voss, Carola
• Stoeger, Tobias
• Neumann, Jens H L
• Hilgendorff, Anne
• Behr, Jürgen
• O'Reilly, Michael
• Lehmann, Mareike
• Burgstaller, Gerald
• Königshoff, Melanie
• Chapman, Harold A
• Theis, Fabian J
• Schiller, Herbert B

Titel

Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis

Ist Teil von

• Nature communications, 2020-07, Vol.11 (1), p.3559-20, Article 3559

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.