{"doi":"10.1016/j.stem.2023.01.009","title":"Kupffer-cell-derived IL-6 is repurposed for hepatocyte dedifferentiation via activating progenitor genes from injury-specific enhancers","abstract":"Stem cell-independent reprogramming of differentiated cells has recently been identified as an important paradigm for repairing injured tissues. Following periportal injury, mature hepatocytes re-activate reprogramming/progenitor-related genes (RRGs) and dedifferentiate into liver progenitor-like cells (LPLCs) in both mice and humans, which contribute remarkably to regeneration. However, it remains unknown which and how external factors trigger hepatocyte reprogramming. Here, by employing single-cell transcriptional profiling and lineage-specific deletion tools, we uncovered that periportal-specific LPLC formation was initiated by regionally activated Kupffer cells but not peripheral monocyte-derived macrophages. Unexpectedly, using in vivo screening, the proinflammatory factor IL-6 was identified as the niche signal repurposed for RRG induction via STAT3 activation, which drove RRG expression through binding to their pre-accessible enhancers. Notably, RRGs were activated through injury-specific rather than liver embryogenesis-related enhancers. Collectively, these findings depict an injury-specific niche signal and the inflammation-mediated transcription in driving the conversion of hepatocytes into a progenitor phenotype.","journal":"Cell stem cell","year":2023,"id":315804,"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":133,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1018075,"name":"Lei Cui","orcid":"0000-0002-4623-7922","position":1,"is_corresponding":false},{"id":592089,"name":"Ping Lin","orcid":"0000-0003-3194-5595","position":2,"is_corresponding":false},{"id":1016335,"name":"Zhaoyuan Liu","orcid":"0000-0002-3117-0833","position":3,"is_corresponding":false},{"id":1019050,"name":"Shujie Bao","orcid":null,"position":4,"is_corresponding":false},{"id":1018076,"name":"Xiaolong Ma","orcid":"0009-0006-5809-8233","position":5,"is_corresponding":false},{"id":1019051,"name":"Haitao Nan","orcid":null,"position":6,"is_corresponding":false},{"id":1018077,"name":"Wencheng Zhu","orcid":"0000-0001-8123-9504","position":7,"is_corresponding":false},{"id":1019052,"name":"Jin Cen","orcid":null,"position":8,"is_corresponding":false},{"id":1018078,"name":"Yunuo Mao","orcid":"0009-0009-8695-7834","position":9,"is_corresponding":false},{"id":625131,"name":"Xiong Ma","orcid":"0000-0001-9616-4672","position":10,"is_corresponding":false},{"id":1018079,"name":"Lingyong Jiang","orcid":"0000-0002-1624-4056","position":11,"is_corresponding":false},{"id":660537,"name":"Yu Nie","orcid":"0000-0002-8744-0046","position":12,"is_corresponding":false},{"id":71133,"name":"Florent Ginhoux","orcid":"0000-0002-2857-7755","position":13,"is_corresponding":false},{"id":35608,"name":"Yixue Li","orcid":"0000-0002-1198-7176","position":14,"is_corresponding":false},{"id":1018080,"name":"Li Hong","orcid":"0000-0002-0927-779X","position":15,"is_corresponding":false},{"id":571428,"name":"Lijian Hui","orcid":"0000-0002-6213-6187","position":16,"is_corresponding":false},{"id":811561,"name":"Lu Li","orcid":"0000-0002-7302-8528","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T01:06:32.274501Z","pmid":"36787740","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":[]}