{"doi":"10.1038/s41467-020-17358-3","title":"Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis","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.","journal":"Nature Communications","year":2020,"id":9852,"datarank":0.9881325022237195,"base_score":6.587550014824796,"endowment":6.587550014824796,"self_citation_contribution":0.9881325022237195,"citation_network_contribution":0.0,"self_endowment_contribution":0.9881325022237195,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":725,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.059,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-07-16","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":2925,"name":"Lukas M. 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