{"doi":"10.1242/dev.202249","title":"Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology","abstract":"Ocular lens development entails epithelial to fiber cell differentiation, defects in which cause congenital cataracts. We report the first single-cell multiomic atlas of lens development, leveraging snRNA-seq, snATAC-seq and CUT&RUN-seq to discover previously unreported mechanisms of cell fate determination and cataract-linked regulatory networks. A comprehensive profile of cis- and trans-regulatory interactions, including for the cataract-linked transcription factor MAF, is established across a temporal trajectory of fiber cell differentiation. Furthermore, we identify an epigenetic paradigm of cellular differentiation, defined by progressive loss of the H3K27 methylation writer Polycomb repressive complex 2 (PRC2). PRC2 localizes to heterochromatin domains across master-regulator transcription factor gene bodies, suggesting it safeguards epithelial cell fate. Moreover, we demonstrate that FGF hyper-stimulation in vivo leads to MAF network activation and the emergence of novel lens cell states. Collectively, these data depict a comprehensive portrait of lens fiber cell differentiation, while defining regulatory effectors of cell identity and cataract formation.","journal":"Development","year":2024,"id":430073,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8342,"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":1176697,"name":"Sofia M. Rebull","orcid":null,"position":1,"is_corresponding":false},{"id":1176358,"name":"Erika Grajales‐Esquivel","orcid":"0000-0001-8423-416X","position":2,"is_corresponding":false},{"id":1176698,"name":"Jacob M. Weaver","orcid":null,"position":3,"is_corresponding":false},{"id":1176699,"name":"Stacy Bendezu-Sayas","orcid":null,"position":4,"is_corresponding":false},{"id":1130230,"name":"Michael L. Robinson","orcid":"0000-0003-4779-3426","position":5,"is_corresponding":false},{"id":499776,"name":"Salil A. Lachke","orcid":"0000-0001-8845-010X","position":6,"is_corresponding":false},{"id":1176359,"name":"Katia Del Rio‐Tsonis","orcid":"0000-0002-3051-6716","position":7,"is_corresponding":false},{"id":1176357,"name":"Jared A. Tangeman","orcid":"0000-0002-0224-2893","position":0,"is_corresponding":true}],"reference_count":159,"raw_metadata":null,"created_at":"2026-07-19T01:59:16.092672Z","pmid":"38180241","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":[]}