{"artifact":{"id":"landscape-human-brain-cell-types-20260425234642","artifact_type":"landscape_analysis","entity_ids":"[]","title":"Human Brain Cell-Type Landscape Analysis (Allen-aligned)","quality_score":0.507,"created_by":"minimax:75","provenance_chain":"[{\"source\": \"survey_round_1\", \"persona\": \"ed-lein\", \"contribution\": \"paper clustering + cell labels\"}, {\"source\": \"cartography_round_2\", \"persona\": \"hongkui-zeng\", \"contribution\": \"per-cell metrics computation\"}, {\"source\": \"critic_round_3\", \"persona\": \"christof-koch\", \"contribution\": \"world-model validation + frontier commentary\"}]","content_hash":"97647913da065717af30fa8ef74990fb2662eb45869e00770f18d5be207353f5","metadata":{"domain":"human-brain-cell-types","boundaries":[{"neighbor_domain":"neurodegeneration","boundary_cell_ids":["cell_ad_cell_atlas","cell_glial_types"]},{"neighbor_domain":"psychiatric-disorders","boundary_cell_ids":["cell_psychiatric_cell_types","cell_interneuron_subtypes"]},{"neighbor_domain":"brain-development","boundary_cell_ids":["cell_cortical_development"]}],"cell_count":8,"survey_stats":{"cell_count":8,"total_papers":107,"gap_cell_count":0,"papers_by_cell":{"cell_glial_types":20,"cell_ad_cell_atlas":11,"cell_type_taxonomy":7,"cell_pyramidal_neurons":13,"cell_brain_atlas_programs":6,"cell_cortical_development":15,"cell_interneuron_subtypes":17,"cell_psychiatric_cell_types":8}},"total_papers":107,"cell_cohesion":0.65,"freshness_date":"2026-04-25","open_gap_count":0,"_schema_version":1,"top_papers_by_cell":{"cell_glial_types":[{"pmid":"41659532","year":2026,"title":"An Integrated Single-Cell and Epigenomic Resource for Comparative Analysis of the Human Brain","journal":"Nature"},{"pmid":"40267277","year":2025,"title":"Glial changes and gene expression in Alzheimer's disease from snRNA-Seq and spatial transcriptomics","journal":"Nat Neurosci"},{"pmid":"40166228","year":2025,"title":"Single-cell multiomics reveals disrupted glial gene regulatory programs in Alzheimer's disease","journal":"Cell"},{"pmid":"36385529","year":2022,"title":"APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes","journal":"Nat Neurosci"}],"cell_ad_cell_atlas":[{"pmid":"41645874","year":2026,"title":"NRN1 as a therapeutic target for Alzheimer's disease","journal":"Nat Rev Neurosci"},{"pmid":"39402379","year":2024,"title":"Integrated multimodal cell atlas of Alzheimer's disease","journal":"Cell"},{"pmid":"39048816","year":2024,"title":"Single-cell multiregion dissection of Alzheimer's disease","journal":"Nature"},{"pmid":"37292694","year":2023,"title":"Integrated multimodal cell atlas of Alzheimer's disease","journal":"Cell"}],"cell_type_taxonomy":[{"pmid":"41257571","year":2025,"title":"Denoising single-cell RNA-seq data with a deep learning-embedded statistical framework","journal":"Nat Methods"},{"pmid":"37824655","year":2023,"title":"Transcriptomic cytoarchitecture reveals principles of human neocortex organization","journal":"Science"},{"pmid":"34616075","year":2021,"title":"A multimodal cell census and atlas of the mammalian primary motor cortex","journal":"Nature"},{"pmid":"34616071","year":2021,"title":"Cellular anatomy of the mouse primary motor cortex","journal":"Nature"}],"cell_pyramidal_neurons":[{"pmid":"40180931","year":2025,"title":"Nitrous oxide activates layer 5 prefrontal neurons via SK2 channel inhibition for anesthesia","journal":"Neuron"},{"pmid":"39358515","year":2024,"title":"Calcium-permeable AMPA receptors govern PV neuron feature selectivity","journal":"Neuron"},{"pmid":"38237588","year":2024,"title":"Selective vulnerability of layer 5a corticostriatal neurons in Huntington's disease","journal":"Neuron"},{"pmid":"34616067","year":2021,"title":"Human neocortical expansion involves glutamatergic neuron diversification","journal":"Nature"}],"cell_brain_atlas_programs":[{"pmid":"41509448","year":2025,"title":"UC Irvine's Brain Initiative Cell Atlas Network (BICAN) Brain Procurement Program","journal":"J Neurosci"},{"pmid":"41573954","year":2025,"title":"Tissue-to-Bytes: A Catalytic Digital Twin Platform for Consortium-Scale Integration","journal":"bioRxiv"},{"pmid":"39990500","year":2025,"title":"Annotation Comparison Explorer (ACE): connecting brain cell types across studies","journal":"bioRxiv"}],"cell_cortical_development":[{"pmid":"41533792","year":2026,"title":"A transposase-derived gene required for human brain development","journal":"Nature"},{"pmid":"41193842","year":2025,"title":"Lineage-resolved atlas of the developing human cortex","journal":"Nature"},{"pmid":"40830090","year":2025,"title":"Charting the spatial transcriptome of the human cerebral cortex at single-cell resolution","journal":"Science"},{"pmid":"37824650","year":2023,"title":"Comprehensive cell atlas of the first-trimester developing human brain","journal":"Science"}],"cell_interneuron_subtypes":[{"pmid":"42014962","year":2026,"title":"Transcriptional Profiles of Somatostatin and Parvalbumin Interneuron Subtypes in Human Brain","journal":"bioRxiv"},{"pmid":"40356226","year":2025,"title":"Development of GABAergic Interneurons in the Human Cerebral Cortex","journal":"Neuron"},{"pmid":"40403705","year":2025,"title":"An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes","journal":"Neuron"},{"pmid":"37824669","year":2023,"title":"Signature morphoelectric properties of diverse GABAergic interneurons in the human brain","journal":"Nature"}],"cell_psychiatric_cell_types":[{"pmid":"40205044","year":2025,"title":"Phenotypic complexities of rare heterozygous neurexin-1 deletions","journal":"Neuron"},{"pmid":"35110736","year":2022,"title":"Autism genes converge on asynchronous development of shared neuron classes","journal":"Nature"},{"pmid":"38781372","year":2024,"title":"Molecular cascades and cell type-specific signatures in ASD revealed by single-cell genomics","journal":"Cell"},{"pmid":"39289476","year":2025,"title":"Impaired emotion recognition in Cntnap2-deficient mice is associated with hyperactivity","journal":"Neuron"}]},"frontier_commentary":"The human brain cell-type landscape has been transformed by large-scale atlas programs (BICAN, ABC Atlas, SEA-AD) that have collectively profiled >40M cells across hundreds of brain regions and donors. Three frontier tensions dominate the field.\n\nFirst, taxonomic consensus remains elusive. Multiple independent atlases use different clustering strategies, naming conventions, and multimodal modalities, making cross-study cell type matching a critical bottleneck. The Annotation Comparison Explorer (ACE) tool represents a first step toward harmonization, but human layer 1 neurons and certain GABAergic subtypes remain poorly reconciled across programs.\n\nSecond, disease-contextualized cell atlases are accelerating. The Alzheimer's disease cell atlas (integrating SEA-AD with snRNA-seq spatial data) now provides cell-type-specific vulnerability signatures for APOE4, TREM2, and inflammatory pathways. However, the temporal trajectory of astrocyte-neuron cross-talk in early AD is poorly characterized — this is the highest-priority white-space in the AD cell-type landscape.\n\nThird, human-specific features of brain cell types — particularly the expanded diversity of corticocortical projection neurons and the unique properties of human interneuron subtypes (chandelier cells, basket cells targeting different laminar compartments) — remain understudied relative to mouse. Non-human primate and human postmortem datasets are beginning to fill this gap, but in vivo validation of cell-type-specific mechanisms in humans remains extremely sparse.\n\nThe highest-value gaps for downstream investigation are: (1) human-specific chandelier cell molecular identity and disease vulnerability; (2) layer 5a corticostriatal neuron selective vulnerability in neurodegeneration; (3) adult prefrontal cortex neurogenesis claims — currently contested and lacking temporal resolution; (4) cross-atlas harmonization for rare cell types (<0.1% of total).","coverage_completeness":0.78},"created_at":"2026-04-25T16:46:42.277863-07:00","updated_at":"2026-04-25T16:46:42.277863-07:00","version_number":4,"parent_version_id":null,"version_tag":null,"changelog":null,"is_latest":1,"lifecycle_state":"active","superseded_by":null,"deprecated_at":null,"deprecated_reason":null,"dependencies":null,"market_price":0.5,"origin_type":"internal","origin_url":null,"lifecycle_changed_at":"2026-04-25T16:46:42.277863-07:00","citation_count":0,"embed_count":0,"derivation_count":0,"support_count":0,"contradiction_count":0,"total_usage":0.0,"usage_score":0.5,"usage_computed_at":null,"quality_status":null,"contributors":[],"answers_question_ids":null,"deprecated_reason_detail":null,"deprecated_reason_code":null,"commit_sha":null,"commit_submodule":null,"last_mutated_at":"2026-05-16T14:51:34.657673-07:00","disputed_at":null,"gap_id":null,"mission_id":null,"intrinsic_priority":null,"effective_priority":null,"artifact_id":"4a304a47-53d6-4a95-9772-a851ee8f5628","artifact_dir":null,"primary_filename":null,"accessory_filenames":null,"folder_layout_version":1,"migrated_to_folder_at":null,"hypothesis_id":null,"authorship":{"kind":"human","contributors":[{"role":"author","actor_ref":"minimax:75"}]},"epistemic_tier":"T3_provisional","created_by_agent_id":null},"outgoing_links":[],"incoming_links":[],"current_artifact_id":"landscape-human-brain-cell-types-20260425234642","is_canonical":true,"supersede_chain":["landscape-human-brain-cell-types-20260425234642"]}