{"doi":"10.1101/2022.03.17.484798","title":"Single-cell multiomics atlas of organoid development uncovers longitudinal molecular programs of cellular diversification of the human cerebral cortex","abstract":"Realizing the full utility of brain organoids as experimental systems to study human cortical development requires understanding whether organoids replicate the cellular and molecular events of this complex process precisely, reproducibly, and with fidelity to the embryo. Here we present a comprehensive single-cell transcriptomic, epigenetic, and spatial atlas of human cortical organoid development, comprising over 610,000 cells, spanning initial generation of neural progenitors through production of differentiated neuronal and glial subtypes. We define the lineage relationships and longitudinal molecular trajectories of cortical cell types during development in organoids, and show that developmental processes of cellular diversification in organoids correlate closely to endogenous ones, irrespective of metabolic state. Using this data, we identify genes with predicted human-specific roles in lineage establishment, and discover a developmental origin for the transcriptional diversity of human callosal projection neurons, a population that has undergone dramatic expansion and diversification during human evolution. Our work provides a comprehensive, single-cell molecular map of human corticogenesis in vitro , identifying developmental trajectories and molecular mechanisms associated with human cellular diversification.","journal":null,"year":2022,"id":12152,"datarank":0.9989831558331776,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"self_citation_contribution":0.47032413238937254,"citation_network_contribution":0.5286590234438051,"self_endowment_contribution":0.47032413238937254,"citer_contribution":0.5286590234438051,"corpus_percentile":58.42148087876322,"corpus_rank":512,"citation_count":22,"citer_count":19,"citers_with_citation_signal":18,"citers_with_endowment":18,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.6953,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-03-19","fair_score":24.5833,"fair_percentile":5.870712401055409,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":54474,"name":"Amanda J. Kedaigle","orcid":"0000-0001-6156-5046","position":1,"is_corresponding":false},{"id":54472,"name":"Martina Pigoni","orcid":"0000-0002-7896-6978","position":2,"is_corresponding":false},{"id":2727,"name":"Bruna Paulsen","orcid":"0000-0001-5304-0610","position":3,"is_corresponding":false},{"id":50708,"name":"Xian Adiconis","orcid":"0000-0002-4052-2503","position":4,"is_corresponding":false},{"id":54477,"name":"Kwanho Kim","orcid":"0000-0002-4448-3193","position":5,"is_corresponding":false},{"id":74327,"name":"Tyler Faits","orcid":"0000-0002-7524-6166","position":6,"is_corresponding":false},{"id":80885,"name":"Surya Nagaraja","orcid":"0000-0001-8297-069X","position":7,"is_corresponding":false},{"id":74325,"name":"Noelia Antón-Bolaños","orcid":"0000-0001-6590-4316","position":8,"is_corresponding":false},{"id":79311,"name":"Chiara Gerhardinger","orcid":"0000-0002-6113-0381","position":9,"is_corresponding":false},{"id":54478,"name":"Ashley Tucewicz","orcid":"0000-0002-1735-5735","position":10,"is_corresponding":false},{"id":35220,"name":"Evan Murray","orcid":"0000-0002-9195-7478","position":11,"is_corresponding":false},{"id":11077,"name":"Xin Jin","orcid":"0000-0003-2344-992X","position":12,"is_corresponding":false},{"id":24055,"name":"Fei Chen","orcid":"0000-0003-2308-3649","position":14,"is_corresponding":false},{"id":54476,"name":"Silvia Velasco","orcid":"0000-0003-0638-0932","position":15,"is_corresponding":false},{"id":29633,"name":"Prisca Liberali","orcid":"0000-0003-0695-6081","position":16,"is_corresponding":false},{"id":11089,"name":"Joshua Z. Levin","orcid":"0000-0002-0170-3598","position":17,"is_corresponding":false},{"id":2734,"name":"Paola Arlotta","orcid":"0000-0003-2184-2277","position":18,"is_corresponding":false},{"id":3630,"name":"Jason D. Buenrostro","orcid":"0000-0001-9958-3987","position":19,"is_corresponding":false},{"id":54473,"name":"Ana Uzquiano","orcid":"0000-0003-0696-6087","position":0,"is_corresponding":true}],"reference_count":135,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","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":37.0,"fair_a":48.0,"fair_i":0.0,"fair_r":13.3333,"fair_zscore":-1.8659,"fair_rationale":{"fair_score":24.58,"has_llm":true,"dimensions":{"F":{"name":"Findable","score":37.0,"criteria":[{"key":"f_has_doi","label":"Has a persistent DOI","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"DOI present","rationale":null},{"key":"f_repository_presence","label":"Indexed in repositories / literature DBs","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"datacite=0, pmcid=False, pmid=False","rationale":null},{"key":"f_persistent_ids","label":"Resolvable scholarly identifiers (OpenAlex)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no OpenAlex id","rationale":null},{"key":"f_metadata_richness","label":"Rich, machine-readable metadata","kind":"llm","weight":1.0,"fraction":0.25,"signal":null,"rationale":"The abstract describes the data content (single-cell multiomics, >610,000 cells) but provides no evidence of machine-readable metadata or structured metadata standards."}]},"A":{"name":"Accessible","score":48.0,"criteria":[{"key":"a_open_access","label":"Open Access / files deposited","kind":"deterministic","weight":1.5,"fraction":1.0,"signal":"Open Access","rationale":null},{"key":"a_retrievable","label":"Free full text retrievable","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"0 OA location(s)","rationale":null},{"key":"a_access_protocol","label":"Clear data/code access protocol","kind":"llm","weight":1.0,"fraction":0.0,"signal":null,"rationale":"No mention of any data repository, URL, or access protocol for the data or code is present in the provided text."}]},"I":{"name":"Interoperable","score":0.0,"criteria":[{"key":"i_linked_data","label":"Linked datasets / DataCite relations","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"linked_datasets=0, datacite=0","rationale":null},{"key":"i_standard_ids","label":"References data via standard accessions","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"accessions=0, trials=0","rationale":null},{"key":"i_standards","label":"Standard formats, vocabularies & identifiers","kind":"llm","weight":1.0,"fraction":0.0,"signal":null,"rationale":"The text does not specify any standard formats, ontologies, or identifiers used for the single-cell data."}]},"R":{"name":"Reusable","score":13.33,"criteria":[{"key":"r_license","label":"Clear, open reuse license","kind":"deterministic","weight":1.5,"fraction":0.0,"signal":"no license","rationale":null},{"key":"r_downloads","label":"Demonstrated reuse (downloads)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"downloads=0","rationale":null},{"key":"r_version","label":"Versioned / maintained","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no version chain","rationale":null},{"key":"r_dataset","label":"Classified as a data resource","kind":"deterministic","weight":0.5,"fraction":1.0,"signal":"is_dataset","rationale":null},{"key":"r_reusability","label":"Data-availability statement, license & reproducibility","kind":"llm","weight":2.0,"fraction":0.0,"signal":null,"rationale":"No data availability statement, software/code availability, license, or reproducibility details are provided in the abstract."}]}},"suggestions":["Deposit raw and processed single-cell data in a public repository (e.g., GEO, ArrayExpress, or CellxGene) with a persistent identifier and machine-readable metadata.","Provide a clear data availability statement in the manuscript specifying repository accession numbers and any restrictions.","Include a code availability section with a link to the analysis code (e.g., GitHub) and a license (e.g., MIT or CC-BY).","Adopt community standard file formats (e.g., HDF5 for expression matrices, BAM for aligned reads) and standard ontologies (e.g., Cell Ontology for cell types).","Add a reproducibility section describing computational environment, key parameters, and version numbers of software packages."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v2","fulltext_source":"abstract_only"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v2","fair_fulltext_source":"abstract_only","fair_has_llm":true,"fair_computed_at":"2026-06-18T00:47:18.483592Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}