{"doi":"10.1016/j.cell.2024.05.030","title":"TNF-NF-κB-p53 axis restricts in vivo survival of hPSC-derived dopamine neurons","abstract":"Ongoing, early-stage clinical trials illustrate the translational potential of human pluripotent stem cell (hPSC)-based cell therapies in Parkinson's disease (PD). However, an unresolved challenge is the extensive cell death following transplantation. Here, we performed a pooled CRISPR-Cas9 screen to enhance postmitotic dopamine neuron survival in vivo. We identified p53-mediated apoptotic cell death as a major contributor to dopamine neuron loss and uncovered a causal link of tumor necrosis factor alpha (TNF-α)-nuclear factor κB (NF-κB) signaling in limiting cell survival. As a translationally relevant strategy to purify postmitotic dopamine neurons, we identified cell surface markers that enable purification without the need for genetic reporters. Combining cell sorting and treatment with adalimumab, a clinically approved TNF-α inhibitor, enabled efficient engraftment of postmitotic dopamine neurons with extensive reinnervation and functional recovery in a preclinical PD mouse model. Thus, transient TNF-α inhibition presents a clinically relevant strategy to enhance survival and enable engraftment of postmitotic hPSC-derived dopamine neurons in PD.","journal":"Cell","year":2024,"id":418077,"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":56,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"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":271974,"name":"So Yeon Koo","orcid":"0000-0001-8634-7643","position":1,"is_corresponding":false},{"id":1163616,"name":"Markus Rießland","orcid":"0000-0003-2592-5045","position":2,"is_corresponding":false},{"id":16907,"name":"Fayzan Chaudhry","orcid":"0000-0002-4295-8570","position":3,"is_corresponding":false},{"id":1163617,"name":"Benjamin Kolisnyk","orcid":"0000-0003-3990-0340","position":4,"is_corresponding":false},{"id":571171,"name":"Hyunwoo Cho","orcid":"0000-0003-3166-585X","position":5,"is_corresponding":false},{"id":865616,"name":"Marco Russo","orcid":"0000-0002-0550-0608","position":6,"is_corresponding":false},{"id":554398,"name":"Nathalie Saurat","orcid":"0000-0002-6439-5166","position":7,"is_corresponding":false},{"id":877790,"name":"Sanjoy Mehta","orcid":"0009-0006-8991-8425","position":8,"is_corresponding":false},{"id":877792,"name":"Ralph Garippa","orcid":"0000-0003-3917-0739","position":9,"is_corresponding":false},{"id":53879,"name":"Doron Betel","orcid":"0000-0002-8006-7752","position":10,"is_corresponding":false},{"id":109231,"name":"Lorenz Studer","orcid":"0000-0003-0741-7987","position":11,"is_corresponding":false},{"id":109216,"name":"Tae Wan Kim","orcid":"0000-0002-0831-6881","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T01:57:02.483590Z","pmid":"38866017","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":[]}