{"doi":"10.1016/j.stemcr.2024.11.014","title":"Heparan sulfate regulates the fate decisions of human pluripotent stem cells","abstract":"Heparan sulfate (HS) is an anionic polysaccharide generated by all animal cells, but our understanding of its roles in human pluripotent stem cell (hPSC) self-renewal and differentiation is limited. We derived HS-deficient hPSCs by disrupting the EXT1 glycosyltransferase. These EXT1 −/− hPSCs maintain self-renewal and pluripotency under standard culture conditions that contain high levels of basic fibroblast growth factor(bFGF), a requirement for sufficient bFGF signaling in the engineered cells. Intriguingly, Activin/Nodal signaling is also compromised in EXT1 −/− hPSCs, highlighting HS's previously unexplored involvement in this pathway. As a result, EXT1 −/− hPSCs fail to differentiate into mesoderm or endoderm lineages. Unexpectedly, HS is dispensable for early ectodermal differentiation of hPSCs but still critical in generating motor neurons. Those derived from HS-deficient hPSCs lack proper neuronal projections and show alterations in axonogenesis gene expression. Thus, our study uncovers expected and unexpected mechanistic roles of HS in hPSC fate decisions.","journal":"Stem Cell Reports","year":2024,"id":470255,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"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":1304300,"name":"Deena Al Mahbuba","orcid":"0000-0003-1951-6165","position":1,"is_corresponding":false},{"id":591913,"name":"Sayaka Masuko","orcid":"0000-0002-9072-0356","position":2,"is_corresponding":false},{"id":141487,"name":"Qiao Li","orcid":null,"position":3,"is_corresponding":false},{"id":1304301,"name":"Andrew C. Elton","orcid":"0000-0003-4388-5227","position":4,"is_corresponding":false},{"id":635947,"name":"Yefim Zaltsman","orcid":"0000-0002-2979-8197","position":5,"is_corresponding":false},{"id":270301,"name":"Paul J. Wrighton","orcid":"0000-0002-0354-0278","position":6,"is_corresponding":false},{"id":288980,"name":"Ke Xia","orcid":"0000-0001-9699-9901","position":7,"is_corresponding":false},{"id":288978,"name":"Xiaorui Han","orcid":"0000-0001-9510-4838","position":8,"is_corresponding":false},{"id":744769,"name":"Yilan Ouyang","orcid":"0000-0001-5373-310X","position":9,"is_corresponding":false},{"id":233177,"name":"Fuming Zhang","orcid":"0000-0003-2803-3704","position":10,"is_corresponding":false},{"id":286697,"name":"Robert J. Linhardt","orcid":"0000-0003-2219-5833","position":11,"is_corresponding":false},{"id":44842,"name":"Laura L. Kiessling","orcid":"0000-0001-6829-1500","position":12,"is_corresponding":false},{"id":454698,"name":"Deepsing Syangtan","orcid":"0000-0001-5245-4782","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T02:05:36.656771Z","pmid":"39729990","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":[]}