{"doi":"10.1101/2024.03.22.586316","title":"Single-cell epigenomic dysregulation of Systemic Sclerosis fibroblasts via CREB1/EGR1 axis in self-assembled human skin equivalents","abstract":"3D skin-like tissue model of SSc, and now analyze the transcriptomic (scRNA-seq) and epigenetic (scATAC-seq) characteristics of this model at single-cell resolution. SSc 3D skin-like tissues were fabricated using autologous fibroblasts, macrophages, and plasma from SSc patients or healthy control (HC) donors. SSc tissues displayed increased dermal thickness and contractility, as well as increased α-SMA staining. Single-cell transcriptomic and epigenomic analyses identified keratinocytes, macrophages, and five populations of fibroblasts (labeled FB1 - 5). Notably, FB1 APOE-expressing fibroblasts were 12-fold enriched in SSc tissues and were characterized by high EGR1 motif accessibility. Pseudotime analysis suggests that FB1 fibroblasts differentiate from a TGF-β1-responsive fibroblast population and ligand-receptor analysis indicates that the FB1 fibroblasts are active in macrophage crosstalk via soluble ligands including FGF2 and APP. These findings provide characterization of the 3D skin-like model at single cell resolution and establish that it recapitulates subsets of fibroblasts and macrophage phenotypes observed in skin biopsies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":486869,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.824,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":894239,"name":"Noelle N. Kosarek","orcid":"0000-0001-6136-0286","position":1,"is_corresponding":false},{"id":1265596,"name":"Rezvan Parvizi","orcid":"0000-0001-8650-1225","position":2,"is_corresponding":false},{"id":1330961,"name":"Helen Jarnagin","orcid":null,"position":3,"is_corresponding":false},{"id":488264,"name":"Gretel M. Torres","orcid":"0000-0002-1932-7383","position":4,"is_corresponding":false},{"id":488263,"name":"Rajan Bhandari","orcid":"0000-0001-9336-955X","position":5,"is_corresponding":false},{"id":900667,"name":"Mengqi Huang","orcid":"0000-0002-1675-8575","position":6,"is_corresponding":false},{"id":516383,"name":"Diana M. Toledo","orcid":"0000-0002-7501-8286","position":7,"is_corresponding":false},{"id":630229,"name":"Avi Smith","orcid":"0000-0002-8904-7539","position":8,"is_corresponding":false},{"id":1053832,"name":"Dillon Popovich","orcid":"0000-0002-3015-4030","position":9,"is_corresponding":false},{"id":766630,"name":"Michael Mariani","orcid":"0000-0001-5852-0517","position":10,"is_corresponding":false},{"id":894673,"name":"Hee-Taek Yang","orcid":null,"position":11,"is_corresponding":false},{"id":7271,"name":"Tammara Wood","orcid":"0000-0002-4370-1398","position":12,"is_corresponding":false},{"id":630230,"name":"Jonathan A. Garlick","orcid":"0009-0008-9500-6435","position":13,"is_corresponding":false},{"id":7277,"name":"Patricia A. Pioli","orcid":"0000-0001-6896-7259","position":14,"is_corresponding":false},{"id":7279,"name":"Michael L. Whitfield","orcid":"0000-0002-0862-6003","position":15,"is_corresponding":false},{"id":1330960,"name":"Tamar R. Abel","orcid":null,"position":0,"is_corresponding":true}],"reference_count":116,"raw_metadata":null,"created_at":"2026-07-19T02:08:01.404471Z","pmid":"38585776","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":[]}