{"doi":"10.1016/j.stemcr.2022.10.007","title":"Notch activation during early mesoderm induction modulates emergence of the T/NK cell lineage from human iPSCs","abstract":"A robust method of producing mature T cells from iPSCs is needed to realize their therapeutic potential. NOTCH1 is known to be required for the production of hematopoietic progenitor cells with T cell potential in vivo . Here we identify a critical window during mesodermal differentiation when Notch activation robustly improves access to definitive hematopoietic progenitors with T/NK cell lineage potential. Low-density progenitors on either OP9-hDLL4 feeder cells or hDLL4-coated plates favored T cell maturation into TCRab + CD3 + CD8 + cells that express expected T cell markers, upregulate activation markers, and proliferate in response to T cell stimulus. Single-cell RNAseq shows Notch activation yields a 6-fold increase in multi-potent hematopoietic progenitors that follow a developmental trajectory toward T cells with clear similarity to post-natal human thymocytes. We conclude that early mesodermal Notch activation during hematopoietic differentiation is a missing stimulus with broad implications for producing hematopoietic progenitors with definitive characteristics.","journal":"Stem Cell Reports","year":2022,"id":275948,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":946581,"name":"Seonmi Park","orcid":null,"position":1,"is_corresponding":false},{"id":820704,"name":"Andrew McCracken","orcid":"0000-0002-6523-5295","position":2,"is_corresponding":false},{"id":946582,"name":"Mona Haratianfar","orcid":null,"position":3,"is_corresponding":false},{"id":946024,"name":"Jonathan Lindstrom","orcid":"0009-0005-8303-1025","position":4,"is_corresponding":false},{"id":89670,"name":"Carlos Villacorta-Martín","orcid":"0000-0002-1350-465X","position":5,"is_corresponding":false},{"id":254892,"name":"Aditya Mithal","orcid":"0000-0002-8165-7674","position":6,"is_corresponding":false},{"id":880828,"name":"Feiya Wang","orcid":"0000-0002-7507-6275","position":7,"is_corresponding":false},{"id":609953,"name":"Meng Yang","orcid":"0000-0002-8060-401X","position":8,"is_corresponding":false},{"id":340206,"name":"George J. Murphy","orcid":"0000-0003-3464-793X","position":9,"is_corresponding":false},{"id":253657,"name":"Gustavo Mostoslavsky","orcid":"0000-0002-0784-2169","position":10,"is_corresponding":false},{"id":253648,"name":"Dar Heinze","orcid":"0000-0003-1683-1178","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T00:28:26.545826Z","pmid":"36332629","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":[]}