{"doi":"10.7554/elife.70992","title":"Wnt signaling mediates acquisition of blood–brain barrier properties in naïve endothelium derived from human pluripotent stem cells","abstract":"Endothelial cells (ECs) in the central nervous system (CNS) acquire their specialized blood–brain barrier (BBB) properties in response to extrinsic signals, with Wnt/β-catenin signaling coordinating multiple aspects of this process. Our knowledge of CNS EC development has been advanced largely by animal models, and human pluripotent stem cells (hPSCs) offer the opportunity to examine BBB development in an in vitro human system. Here, we show that activation of Wnt signaling in hPSC-derived naïve endothelial progenitors, but not in matured ECs, leads to robust acquisition of canonical BBB phenotypes including expression of GLUT-1, increased claudin-5, decreased PLVAP, and decreased permeability. RNA-seq revealed a transcriptome profile resembling ECs with CNS-like characteristics, including Wnt-upregulated expression of LEF1 , APCDD1 , and ZIC3 . Together, our work defines effects of Wnt activation in naïve ECs and establishes an improved hPSC-based model for interrogation of CNS barriergenesis.","journal":"eLife","year":2021,"id":150207,"datarank":1.9422410037455076,"base_score":4.574710978503383,"endowment":4.574710978503383,"self_citation_contribution":0.6862066467755076,"citation_network_contribution":1.25603435697,"self_endowment_contribution":0.6862066467755076,"citer_contribution":1.25603435697,"corpus_percentile":null,"corpus_rank":null,"citation_count":96,"citer_count":79,"citers_with_citation_signal":59,"citers_with_endowment":59,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9476,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE173206","GSM3040844 GSM3040845 GSM3040852 GSM3040853 GSM3040858 GSM3040859 GSM3040864 GSM3040865","GSM2498580 GSM2498581 GSM2498582 GSM2498583 GSM2498584 GSM2498585 GSM2498586 GSM2498587","GSM3455653 GSM3455654 GSM3455657 GSM3455658 GSM3455661 GSM3455662 GSM3455665 SM3455666","GSM4160534 GSM4160535 GSM4160536 GSM4160537 GSM4160538 GSM4160539 GSM4160540 GSM4160541 GSM4160542 GSM4160543","GSM3980129 GSM4008656 GSM4008657 GSM4008658","GSE76381","GSE119212"]},"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":279346,"name":"Hideaki Nishihara","orcid":"0000-0002-2990-835X","position":1,"is_corresponding":false},{"id":639558,"name":"Scott G Canfield","orcid":null,"position":2,"is_corresponding":false},{"id":639559,"name":"Koji L Foreman","orcid":null,"position":3,"is_corresponding":false},{"id":279353,"name":"Britta Engelhardt","orcid":"0000-0003-3059-9846","position":4,"is_corresponding":false},{"id":254957,"name":"Sean P. Palecek","orcid":"0000-0003-4917-5584","position":5,"is_corresponding":false},{"id":254958,"name":"Eric V. Shusta","orcid":"0000-0002-4297-0158","position":6,"is_corresponding":false},{"id":254955,"name":"Benjamin D. Gastfriend","orcid":"0000-0002-4677-1455","position":0,"is_corresponding":true}],"reference_count":105,"raw_metadata":null,"created_at":"2026-07-18T23:43:01.325389Z","pmid":"34755601","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":[]}