{"doi":"10.17615/rmns-jr16","title":"Paracrine signals from mesenchymal cell populations govern the expansion and differentiation of human hepatic stem cells to adult liver fates","abstract":"Differentiation of embryonic or determined stem cell populations to adult liver fates under known conditions yields cells with some but not other adult-specific genes, aberrant regulation of one or more genes, and variation in the results from experiment to experiment. We tested the hypothesis that sets of signals produced by freshly isolated, lineage-dependent mesenchymal cell populations would yield greater efficiency and reproducibility in driving differentiation of human hepatic stem cells (hHpSCs) to adult liver fates. Subpopulations of liver-derived mesenchymal cells, purified by immunoselection technologies, included 1) angioblasts; 2) mature endothelia; 3) hepatic stellate cell precursors; 4) mature stellate cells (pericytes) and 5) myofibroblasts. Freshly immunoselected cells of each of these subpopulations were established in primary cultures under wholly defined (serum-free) conditions that we developed for short-term cultures and used them as feeders with hHpSCs. Feeders of angioblasts yielded self-replication; stellate cell precursors caused lineage restriction to hepatoblasts; mature endothelia produced differentiation to hepatocytes; and mature stellate cells and/or myofibroblasts resulted in differentiation to cholangiocytes. Paracrine signals, produced by the different feeders, were identified by biochemical, immunohistochemical, and qRT-PCR analyses and then those signals were used to replace the feeders in monolayer and 3-D cultures to elicit the desired biological responses from the hHpSCs. The defined paracrine signals proved able to yield reproducible responses from the hHpSCs and to permit differentiation to fully mature and functional parenchymal cells.","journal":"UNC Libraries","year":2020,"id":111556,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9461,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":528959,"name":"Yunfang Wang","orcid":"0000-0003-4446-6059","position":1,"is_corresponding":false},{"id":229779,"name":"Mitsuo Yamauchi","orcid":null,"position":2,"is_corresponding":false},{"id":528960,"name":"Lola M. Reid","orcid":"0000-0001-5956-6242","position":3,"is_corresponding":false},{"id":528961,"name":"Nicholas Moss","orcid":"0009-0007-3830-8173","position":4,"is_corresponding":false},{"id":529795,"name":"Hsin-Lei Yao","orcid":null,"position":5,"is_corresponding":false},{"id":491590,"name":"David A. Gerber","orcid":"0000-0002-7972-5228","position":6,"is_corresponding":false},{"id":529796,"name":"Cui, Cai-Bin","orcid":null,"position":7,"is_corresponding":false},{"id":529797,"name":"Martin J. Costello","orcid":null,"position":8,"is_corresponding":false},{"id":449328,"name":"Marnisa Sricholpech","orcid":"0000-0003-2139-0688","position":9,"is_corresponding":false},{"id":529798,"name":"Eliane Wauthier","orcid":null,"position":10,"is_corresponding":false},{"id":471335,"name":"Elizabeth G. Loboa","orcid":"0000-0002-4504-0554","position":11,"is_corresponding":false},{"id":529794,"name":"Claire Barbier","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:05.597252Z","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":[]}