{"doi":"10.1016/j.celrep.2023.112451","title":"Temporal and spatial staging of lung alveolar regeneration is determined by the grainyhead transcription factor Tfcp2l1","abstract":"Alveolar epithelial type 2 (AT2) cells harbor the facultative progenitor capacity in the lung alveolus to drive regeneration after lung injury. Using single-cell transcriptomics, software-guided segmentation of tissue damage, and in vivo mouse lineage tracing, we identified the grainyhead transcription factor cellular promoter 2-like 1 (Tfcp2l1) as a regulator of this regenerative process. Tfcp2l1 loss in adult AT2 cells inhibits self-renewal and enhances AT2-AT1 differentiation during tissue regeneration. Conversely, Tfcp2l1 blunts the proliferative response to inflammatory signaling during the early acute injury phase. Tfcp2l1 temporally regulates AT2 self-renewal and differentiation in alveolar regions undergoing active regeneration. Single-cell transcriptomics and lineage tracing reveal that Tfcp2l1 regulates cell fate dynamics across the AT2-AT1 differentiation and restricts the inflammatory program in murine AT2 cells. Organoid modeling shows that Tfcp2l1 regulation of interleukin-1 (IL-1) receptor expression controlled these cell fate dynamics. These findings highlight the critical role Tfcp2l1 plays in balancing epithelial cell self-renewal and differentiation during alveolar regeneration.","journal":"Cell Reports","year":2023,"id":331494,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":500573,"name":"Derek C. Liberti","orcid":"0000-0003-2991-9283","position":1,"is_corresponding":false},{"id":239737,"name":"John P. Leach","orcid":"0000-0002-0779-8583","position":2,"is_corresponding":false},{"id":239740,"name":"Apoorva Babu","orcid":"0000-0003-3661-5261","position":3,"is_corresponding":false},{"id":96237,"name":"Jonathan Barasch","orcid":"0000-0002-6723-9548","position":4,"is_corresponding":false},{"id":437316,"name":"Tian Shen","orcid":"0000-0001-7064-7051","position":5,"is_corresponding":false},{"id":700876,"name":"Maria Alejandra Diaz‐Miranda","orcid":"0000-0002-6062-8049","position":6,"is_corresponding":false},{"id":239741,"name":"Su Zhou","orcid":"0000-0002-9610-6103","position":7,"is_corresponding":false},{"id":623519,"name":"Yun Ying","orcid":"0000-0003-2306-0949","position":8,"is_corresponding":false},{"id":581649,"name":"Danielle Callaway","orcid":"0000-0002-2395-9818","position":9,"is_corresponding":false},{"id":239739,"name":"Michael P. Morley","orcid":"0000-0002-0958-7376","position":10,"is_corresponding":false},{"id":228733,"name":"Edward E. Morrisey","orcid":"0000-0001-5785-1939","position":11,"is_corresponding":false},{"id":443802,"name":"Fabian L. Cardenas‐Diaz","orcid":"0000-0002-6504-478X","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T01:09:19.317824Z","pmid":"37119134","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}