{"doi":"10.1101/2021.11.19.469258","title":"Patient induced pluripotent stem cell-derived hepatostellate organoids establish a basis for liver pathologies in telomeropathies","abstract":"Abstract Patients with dyskeratosis congenita (DC) and related telomeropathies resulting from premature telomere dysfunction suffer from multi-organ failure. In the liver, DC patients present with nodular hyperplasia, steatosis, inflammation, and cirrhosis. We model DC liver pathologies using isogenic human induced pluripotent stem (iPS) cells harboring a causal DC mutation in DKC1 , or a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-corrected control allele. Differentiation of these iPS cells into hepatocytes or hepatic stellate cells followed by generation of genotype-admixed hepatostellate organoids revealed a dominant phenotype in the parenchyma, with DC hepatocytes eliciting a pathogenic hyperplastic response in stellate cells independent of stellate cell genotype. Pathogenic phenotypes could be rescued via suppression of AKT activity, a central regulator of MYC-driven hyperplasia downstream of DKC1 mutation. Thus, isogenic iPS-derived admixed hepatostellate organoids offer insight into the liver pathologies in telomeropathies and provide a framework for evaluating emerging therapies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":227764,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9506,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":749419,"name":"Melissa S. Kim","orcid":"0000-0002-7992-7110","position":1,"is_corresponding":false},{"id":475067,"name":"Joshua H. Rhoades","orcid":"0000-0002-1058-0059","position":2,"is_corresponding":false},{"id":277547,"name":"N. M. Johnson","orcid":"0000-0001-7332-0193","position":3,"is_corresponding":false},{"id":307542,"name":"Corbett T. Berry","orcid":"0000-0001-9348-2034","position":4,"is_corresponding":false},{"id":572153,"name":"Sarah Root","orcid":"0000-0001-6845-3020","position":5,"is_corresponding":false},{"id":832064,"name":"Qijun Chen","orcid":"0000-0002-7879-1151","position":6,"is_corresponding":false},{"id":506018,"name":"Yuhua Tian","orcid":"0000-0001-8239-6560","position":7,"is_corresponding":false},{"id":572149,"name":"Rafael Fernández","orcid":"0000-0001-9295-4810","position":8,"is_corresponding":false},{"id":819822,"name":"Zvi Cramer","orcid":"0000-0002-7386-3937","position":9,"is_corresponding":false},{"id":324335,"name":"Stephanie Adams‐Tzivelekidis","orcid":"0000-0002-5642-7439","position":10,"is_corresponding":false},{"id":434621,"name":"Ning Li","orcid":"0000-0001-5997-5556","position":11,"is_corresponding":false},{"id":500618,"name":"F. Brad Johnson","orcid":"0000-0002-7443-7227","position":12,"is_corresponding":false},{"id":307547,"name":"Christopher J. Lengner","orcid":"0000-0002-0574-5189","position":13,"is_corresponding":false},{"id":832063,"name":"Young‐Jun Choi","orcid":"0000-0002-7058-4633","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-18T23:54:46.312854Z","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":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":[]}