{"doi":"10.1101/2022.07.11.499594","title":"Autocrine Sfrp1 inhibits lung fibroblast invasion during transition to injury induced myofibroblasts","abstract":"Fibroblast to myofibroblast conversion is a major driver of tissue remodeling in organ fibrosis. Several distinct lineages of fibroblasts support homeostatic tissue niche functions, yet, specific activation states and phenotypic trajectories of fibroblasts during injury and repair have remained unclear. Here, we combined spatial transcriptomics, longitudinal single-cell RNA-seq and genetic lineage tracing to study fibroblast fates during mouse lung regeneration. We discovered a transitional fibroblast state characterized by high Sfrp1 expression, derived from both Tcf21-Cre lineage positive and negative cells. Sfrp1+ cells appeared early after injury in peribronchiolar, adventitial and alveolar locations and preceded the emergence of myofibroblasts. We identified lineage specific paracrine signals and inferred converging transcriptional trajectories towards Sfrp1+ transitional fibroblasts and Cthrc1+ myofibroblasts. Tgfβ1 downregulated Sfrp1 in non-invasive transitional cells and induced their switch to an invasive Cthrc1+ myofibroblast identity. Finally, using loss of function studies we showed that autocrine Sfrp1 directly inhibits fibroblast invasion by regulating the RhoA pathway. In summary, our study reveals the convergence of spatially and transcriptionally distinct fibroblast lineages into transcriptionally uniform myofibroblasts and identifies Sfrp1 as an autocrine inhibitor of fibroblast invasion during early stages of fibrogenesis.","journal":null,"year":2022,"id":7163,"datarank":0.38474240361923057,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.0,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0475,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-07-12","fair_score":12.5,"fair_percentile":0.15391380826737028,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":64791,"name":"Arunima Sengupta","orcid":"0000-0002-1617-3358","position":1,"is_corresponding":false},{"id":537,"name":"Meshal Ansari","orcid":"0000-0002-8819-7965","position":2,"is_corresponding":false},{"id":49088,"name":"Jeanine C. Pestoni","orcid":null,"position":3,"is_corresponding":false},{"id":64792,"name":"Paulina Ogar","orcid":"0000-0001-7813-8235","position":4,"is_corresponding":false},{"id":540,"name":"Ilias Angelidis","orcid":"0000-0002-0549-8878","position":5,"is_corresponding":false},{"id":27713,"name":"Andreas Liontos","orcid":"0000-0003-0838-3571","position":6,"is_corresponding":false},{"id":64793,"name":"Alberto Rodriguez-Castillo","orcid":null,"position":7,"is_corresponding":false},{"id":4816,"name":"Niklas J. Lang","orcid":"0000-0002-7452-8292","position":8,"is_corresponding":false},{"id":538,"name":"Maximilian Strunz","orcid":null,"position":9,"is_corresponding":false},{"id":64794,"name":"Sara Asgharpour","orcid":null,"position":10,"is_corresponding":false},{"id":49085,"name":"Diana Porras-Gonzalez","orcid":"0009-0000-2858-7921","position":11,"is_corresponding":false},{"id":49094,"name":"Michael Gerckens","orcid":"0000-0002-2251-4382","position":12,"is_corresponding":false},{"id":64795,"name":"Bettina Oehrle","orcid":null,"position":13,"is_corresponding":false},{"id":64796,"name":"Valeria Viteri-Alvarez","orcid":null,"position":14,"is_corresponding":false},{"id":4823,"name":"Isis E. Fernandez","orcid":null,"position":15,"is_corresponding":false},{"id":64797,"name":"Michelle Tallquist","orcid":null,"position":16,"is_corresponding":false},{"id":556,"name":"Martin Irmler","orcid":"0000-0003-3169-479X","position":17,"is_corresponding":false},{"id":564,"name":"Johannes Beckers","orcid":"0000-0001-7874-3822","position":18,"is_corresponding":false},{"id":572,"name":"Oliver Eickelberg","orcid":"0000-0001-7170-0360","position":19,"is_corresponding":false},{"id":64798,"name":"Gabriel Mircea Stoleriu","orcid":null,"position":20,"is_corresponding":false},{"id":33096,"name":"Juergen Behr","orcid":"0000-0002-9151-4829","position":21,"is_corresponding":false},{"id":2929,"name":"Nikolaus Kneidinger","orcid":"0000-0001-7583-0453","position":22,"is_corresponding":false},{"id":576,"name":"Ali Önder Yildirim","orcid":"0000-0003-1969-480X","position":23,"is_corresponding":false},{"id":64799,"name":"Katrin Ahlbrecht","orcid":"0000-0003-4200-3739","position":24,"is_corresponding":false},{"id":64800,"name":"Rory E. Morty","orcid":"0000-0003-0833-9749","position":25,"is_corresponding":false},{"id":24378,"name":"Christos Samakovlis","orcid":"0000-0002-9153-6040","position":26,"is_corresponding":false},{"id":42,"name":"Fabian Joachim Theis","orcid":"0000-0002-2419-1943","position":27,"is_corresponding":false},{"id":554,"name":"Gerald Burgstaller","orcid":"0000-0002-7121-2567","position":28,"is_corresponding":false},{"id":573,"name":"Herbert B. Schiller","orcid":"0000-0001-9498-7034","position":29,"is_corresponding":false},{"id":64801,"name":"Alberto Rodríguez-Castillo","orcid":null,"position":30,"is_corresponding":false},{"id":64802,"name":"Michelle D. Tallquist","orcid":"0000-0002-1383-144X","position":31,"is_corresponding":false},{"id":578,"name":"Christoph H. Mayr","orcid":"0000-0001-5353-4768","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"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":20.0,"fair_a":30.0,"fair_i":0.0,"fair_r":0.0,"fair_zscore":-2.9589,"fair_rationale":{"fair_score":12.5,"has_llm":true,"dimensions":{"F":{"name":"Findable","score":20.0,"criteria":[{"key":"f_has_doi","label":"Has a persistent DOI","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"DOI present","rationale":null},{"key":"f_repository_presence","label":"Indexed in repositories / literature DBs","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"datacite=0, pmcid=False, pmid=False","rationale":null},{"key":"f_persistent_ids","label":"Resolvable scholarly identifiers (OpenAlex)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no OpenAlex id","rationale":null},{"key":"f_metadata_richness","label":"Rich, machine-readable metadata","kind":"llm","weight":1.0,"fraction":0.0,"signal":null,"rationale":"The paper does not mention any machine-readable metadata, such as structured data descriptions or standardized metadata schemas."}]},"A":{"name":"Accessible","score":30.0,"criteria":[{"key":"a_open_access","label":"Open Access / files deposited","kind":"deterministic","weight":1.5,"fraction":1.0,"signal":"Open Access","rationale":null},{"key":"a_retrievable","label":"Free full text retrievable","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"0 OA location(s)","rationale":null},{"key":"a_access_protocol","label":"Clear data/code access protocol","kind":"llm","weight":1.0,"fraction":0.0,"signal":null,"rationale":"No protocol for accessing data or code is provided; the text lacks any data or code availability statement."}]},"I":{"name":"Interoperable","score":0.0,"criteria":[{"key":"i_linked_data","label":"Linked datasets / DataCite relations","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"linked_datasets=0, datacite=0","rationale":null},{"key":"i_standard_ids","label":"References data via standard accessions","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"accessions=0, trials=0","rationale":null},{"key":"i_standards","label":"Standard formats, vocabularies & identifiers","kind":"llm","weight":1.0,"fraction":0.0,"signal":null,"rationale":"The paper does not specify use of standard formats, controlled vocabularies, or persistent identifiers for data or code."}]},"R":{"name":"Reusable","score":0.0,"criteria":[{"key":"r_license","label":"Clear, open reuse license","kind":"deterministic","weight":1.5,"fraction":0.0,"signal":"no license","rationale":null},{"key":"r_downloads","label":"Demonstrated reuse (downloads)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"downloads=0","rationale":null},{"key":"r_version","label":"Versioned / maintained","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no version chain","rationale":null},{"key":"r_dataset","label":"Classified as a data resource","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"not a dataset","rationale":null},{"key":"r_reusability","label":"Data-availability statement, license & reproducibility","kind":"llm","weight":2.0,"fraction":0.0,"signal":null,"rationale":"There is no data-availability statement, license, or description of reproducibility measures in the provided text."}]}},"suggestions":["Include a data-availability statement specifying where raw and processed data (e.g., sequencing data) are deposited, with accession numbers.","Provide a code repository (e.g., GitHub) with analysis scripts and a software environment description (e.g., Docker or conda).","Use standardized file formats (e.g., FASTQ, BAM, HDF5) and controlled vocabularies (e.g., Cell Ontology) for cell types.","Add a license (e.g., CC-BY 4.0) to the data and code to clarify reuse permissions.","Describe metadata using a community standard (e.g., ISA-Tab or BioStudies) to enhance findability and interoperability."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v1","fulltext_source":"abstract_only"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v1","fair_fulltext_source":"abstract_only","fair_has_llm":true,"fair_computed_at":"2026-06-14T20:31:34.980793Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}