{"doi":"10.1101/2022.04.22.488753","title":"Benchmarking brain organoid recapitulation of fetal corticogenesis","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>\n                  Brain organoids are becoming increasingly relevant to dissect the molecular mechanisms underlying psychiatric and neurological conditions. The\n                  <jats:italic>in vitro</jats:italic>\n                  recapitulation of key features of human brain development affords the unique opportunity of investigating the developmental antecedents of neuropsychiatric conditions in the context of the actual patients’ genetic backgrounds. Specifically, multiple strategies of brain organoid (BO) differentiation have enabled the investigation of human cerebral corticogenesis\n                  <jats:italic>in vitro</jats:italic>\n                  with increasing accuracy. However, the field lacks a systematic investigation of how closely the gene co-expression patterns seen in cultured BO from different protocols match those observed in fetal cortex, a paramount information for ensuring the sensitivity and accuracy of modeling disease trajectories. Here we benchmark BO against fetal corticogenesis by integrating transcriptomes from in-house differentiated cortical BO (CBO), other BO systems, human fetal brain samples processed in-house, and prenatal cortices from the BrainSpan Atlas. We identified co-expression patterns and prioritized hubs of human corticogenesis and CBO differentiation, highlighting both well-preserved and discordant trends across BO protocols, including different degrees of heterochronicity in differentiation across BO models compared to fetal cortex. Our approach provides a framework to directly compare the extent of\n                  <jats:italic>in vivo/in vitro</jats:italic>\n                  alignment of neurodevelopmentally relevant processes and their attending temporalities, structured as an accessible resource to query for modelling human corticogenesis and the neuropsychiatric outcomes of its alterations.\n                </jats:p>","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":null,"id":16998,"datarank":0.3227592769035515,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.030872754545254434,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.030872754545254434,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":3,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":44801,"name":"Sebastiano Trattaro","orcid":"0000-0002-3142-6747","position":1,"is_corresponding":false},{"id":123242,"name":"Nicolò Caporale","orcid":null,"position":2,"is_corresponding":false},{"id":123243,"name":"Alejandro López-Tobón","orcid":null,"position":3,"is_corresponding":false},{"id":123244,"name":"Erika Tenderini","orcid":null,"position":4,"is_corresponding":false},{"id":123245,"name":"Flavia Troglio","orcid":null,"position":5,"is_corresponding":false},{"id":123246,"name":"Michele Gabriele","orcid":null,"position":6,"is_corresponding":false},{"id":123247,"name":"Raul Bardini Bressan","orcid":null,"position":7,"is_corresponding":false},{"id":123248,"name":"Steven M Pollard","orcid":null,"position":8,"is_corresponding":false},{"id":123249,"name":"William T Gibson","orcid":"0000-0002-6552-402X","position":9,"is_corresponding":false},{"id":40568,"name":"Giuseppe Testa","orcid":"0000-0002-9104-0918","position":10,"is_corresponding":false},{"id":44796,"name":"Cristina Cheroni","orcid":"0000-0002-0832-2333","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24259432","pmcid":null,"openalex_id":"https://openalex.org/W4280649170","authors":[],"funders":[{"funder_name":"European Commission","grant_id":"825759","title":"Novel Testing Strategies for Endocrine Disruptors in the Context of Developmental NeuroToxicity"},{"funder_name":"Wellcome Trust","grant_id":"unidentified","title":"unidentified"},{"funder_name":"European Commission","grant_id":"616441","title":"Modeling Disease through Cell Reprogramming: a Translational Approach to the Pathogenesis of Syndromes Caused by Symmetrical Gene Dosage Imbalances"}],"total_grants":3,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2022,"count":2},{"year":2023,"count":1},{"year":2024,"count":2},{"year":2025,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2022/04/22/2022.04.22.488753.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2022/04/22/2022.04.22.488753.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2022.04.22.488753","host_type":"publisher"},{"url":"https://doi.org/10.1101/2022.04.22.488753","host_type":"repository"}],"fields_of_study":["Epigenetics and DNA Methylation","Neonatal Respiratory Health Research","Single-cell and spatial transcriptomics","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":[],"keywords":["Corticogenesis","Organoid","Human brain","Neuroscience","Biology","Context (archaeology)","Lissencephaly","Cerebral cortex","Computational biology","Genetics","Gene","Embryonic stem cell"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-02T15:31:57.305195Z","pmid":null,"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":[]}