{"doi":"10.1101/2023.10.24.563664","title":"A Spatiotemporal and Machine-Learning Platform Accelerates the Manufacturing of hPSC-derived Esophageal Mucosa","abstract":"ABSTRACT Human pluripotent stem cell-derived tissue engineering offers great promise in designer cell-based personalized therapeutics. To harness such potential, a broader approach requires a deeper understanding of tissue-level interactions. We previously developed a manufacturing system for the ectoderm-derived skin epithelium for cell replacement therapy. However, it remains challenging to manufacture the endoderm-derived esophageal epithelium, despite both possessing similar stratified structure. Here we employ single cell and spatial technologies to generate a spatiotemporal multi-omics cell atlas for human esophageal development. We illuminate the cellular diversity, dynamics and signal communications for the developing esophageal epithelium and stroma. Using the machine-learning based Manatee, we prioritize the combinations of candidate human developmental signals for in vitro derivation of esophageal basal cells. Functional validation of the Manatee predictions leads to a clinically-compatible system for manufacturing human esophageal mucosa. Our approach creates a versatile platform to accelerate human tissue manufacturing for future cell replacement therapies to treat human genetic defects and wounds.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":401309,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"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":1178281,"name":"Carmel Grace McCullough","orcid":null,"position":1,"is_corresponding":false},{"id":555778,"name":"Lucas Seninge","orcid":"0000-0001-6536-6810","position":2,"is_corresponding":false},{"id":861827,"name":"Lihao Guo","orcid":"0009-0001-6431-176X","position":3,"is_corresponding":false},{"id":1178282,"name":"Woo-Joo Kwon","orcid":null,"position":4,"is_corresponding":false},{"id":1177967,"name":"Yongchun Zhang","orcid":"0009-0009-9949-0604","position":5,"is_corresponding":false},{"id":669298,"name":"Nancy Yanzhe Li","orcid":"0000-0001-6217-5234","position":6,"is_corresponding":false},{"id":278895,"name":"Sadhana Gaddam","orcid":"0000-0001-6477-0483","position":7,"is_corresponding":false},{"id":1056232,"name":"Cory Pan","orcid":"0000-0003-1808-6239","position":8,"is_corresponding":false},{"id":1108670,"name":"Hanson H. Zhen","orcid":null,"position":9,"is_corresponding":false},{"id":1162290,"name":"Jessica L. Torkelson","orcid":"0000-0002-1569-803X","position":10,"is_corresponding":false},{"id":104361,"name":"Ian A. Glass","orcid":"0000-0001-6762-8407","position":11,"is_corresponding":false},{"id":1178283,"name":"Greg Charville","orcid":null,"position":12,"is_corresponding":false},{"id":75510,"name":"Jianwen Que","orcid":"0000-0002-6540-6701","position":13,"is_corresponding":false},{"id":266953,"name":"Joshua M. Stuart","orcid":"0000-0002-2171-565X","position":14,"is_corresponding":false},{"id":491708,"name":"Hongxu Ding","orcid":"0000-0002-7846-9744","position":15,"is_corresponding":false},{"id":317845,"name":"Anthony E. Oro","orcid":"0000-0002-6261-138X","position":16,"is_corresponding":false},{"id":281424,"name":"Ying Yang","orcid":"0000-0002-4197-6216","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-19T01:20:08.195423Z","pmid":"37961271","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":[]}