{"doi":"10.1016/j.celrep.2023.112012","title":"TRIM28 secures skeletal stem cell fate during skeletogenesis by silencing neural gene expression and repressing GREM1/AKT/mTOR signaling axis","abstract":"Long bones are generated by mesoderm-derived skeletal progenitor/stem cells (SSCs) through endochondral ossification, a process of sequential chondrogenic and osteogenic differentiation tightly controlled by the synergy between intrinsic and microenvironment cues. Here, we report that loss of TRIM28, a transcriptional corepressor, in mesoderm-derived cells expands the SSC pool, weakens SSC osteochondrogenic potential, and endows SSCs with properties of ectoderm-derived neural crest cells (NCCs), leading to severe defects of skeletogenesis. TRIM28 preferentially enhances H3K9 trimethylation and DNA methylation on chromatin regions more accessible in NCCs; loss of this silencing upregulates neural gene expression and enhances neurogenic potential. Moreover, TRIM28 loss causes hyperexpression of GREM1, which is an extracellular signaling factor promoting SSC self-renewal and SSC neurogenic potential by activating AKT/mTORC1 signaling. Our results suggest that TRIM28-mediated chromatin silencing establishes a barrier for maintaining the SSC lineage trajectory and preventing a transition to ectodermal fate by regulating both intrinsic and microenvironment cues.","journal":"Cell Reports","year":2023,"id":380152,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"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":760771,"name":"Ye Liu","orcid":"0000-0002-4845-6643","position":1,"is_corresponding":false},{"id":582528,"name":"Seung‐Gi Jin","orcid":"0000-0001-5041-0559","position":2,"is_corresponding":false},{"id":356260,"name":"Jennifer Johnson","orcid":"0000-0002-2061-4814","position":3,"is_corresponding":false},{"id":385878,"name":"Hongwen Xuan","orcid":"0000-0002-4095-6352","position":4,"is_corresponding":false},{"id":1145265,"name":"Di Lu","orcid":"0000-0003-1040-7763","position":5,"is_corresponding":false},{"id":1145266,"name":"Jianshuang Li","orcid":"0000-0002-7344-7896","position":6,"is_corresponding":false},{"id":777377,"name":"Lukai Zhai","orcid":"0000-0001-5880-6750","position":7,"is_corresponding":false},{"id":1145267,"name":"Xianfeng Li","orcid":"0000-0002-3364-4051","position":8,"is_corresponding":false},{"id":911770,"name":"Yaguang Zhao","orcid":null,"position":9,"is_corresponding":false},{"id":1057337,"name":"Minmin Liu","orcid":"0000-0002-7405-8972","position":10,"is_corresponding":false},{"id":444950,"name":"Sonya Craig","orcid":"0000-0002-2535-4951","position":11,"is_corresponding":false},{"id":911769,"name":"Joseph S. Floramo","orcid":null,"position":12,"is_corresponding":false},{"id":760772,"name":"Vladimir Molchanov","orcid":"0000-0002-8492-8548","position":13,"is_corresponding":false},{"id":942289,"name":"Jie Li","orcid":"0000-0002-4734-1940","position":14,"is_corresponding":false},{"id":1145268,"name":"Jia‐Da Li","orcid":"0000-0002-4236-3518","position":15,"is_corresponding":false},{"id":984137,"name":"Connie M. Krawczyk","orcid":"0000-0002-2468-5986","position":16,"is_corresponding":false},{"id":329463,"name":"Xiaobing Shi","orcid":"0000-0001-5242-8189","position":17,"is_corresponding":false},{"id":184026,"name":"Gerd P. Pfeifer","orcid":"0000-0002-5080-9604","position":18,"is_corresponding":false},{"id":760773,"name":"Tao Yang","orcid":"0000-0002-9856-9929","position":19,"is_corresponding":false},{"id":911099,"name":"Huadie Liu","orcid":"0000-0003-0121-5727","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T01:17:00.789848Z","pmid":"36680774","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":[]}