{"slug":"cell","open_questions":[{"id":"open_question-4d560628-204c-44cf-853e-461357a414db","title":"How do tanycytes interact with pathology?","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-9db7cdbb-a80d-4543-8801-bf8ed228f856","title":"What drives tanycyte senescence?","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-41858ce0-166c-460e-9461-bff9ca862b7d","title":"Can tanycyte function be restored?","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-d458505e-2fae-4130-a341-33c4ce8fecba","title":"How does VTA pathology interact with cortical and limbic Lewy body pathology?","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-2885548b-4d7a-4b0e-8e33-e40beca3c97d","title":"Can we develop therapies that selectively protect or restore VTA function?","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-b3a531f7-cbae-4079-a6a4-28002014b42c","title":"How does VTA pathology contribute to specific non-motor symptoms?","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-456cdc6c-d661-41c6-a872-8ea9399a4df8","title":"How does α-synuclein cause granule cell loss?","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-cell-types-crh-neurons-stress-v2-da3ed3cc","title":"CRHR1 polymorphisms","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-cell-types-crh-neurons-stress-v2-35e3cbbf","title":"Epigenetic markers","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-ad26de8f-6e24-4371-8614-3d86c073907b","title":"Can pharmacological approaches enhance AAC function?","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-ffe88a19-ddde-4464-9e2a-9d69982bac19","title":"What defines selective vulnerability of MS GABAergic neurons?","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-c7bd6442-3ae0-4c3c-8e00-75f955b34a40","title":"What are the molecular mechanisms of cuneate plasticity?","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-d6d658dd-2da8-4691-b58f-668a4e666a78","title":"What are the precise circuit functions of different X94-like subpopulations?","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-c242afed-02ed-450e-8d70-f070873a1208","title":"Can ENS biopsy serve as a definitive diagnostic tool?","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-e3dcdd80-e37c-4b0f-ae07-73e5e53d798a","title":"What is the temporal relationship between cerebellar and cortical pathology?","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-2398e8a9-de73-4475-b7db-f39a83ce2364","title":"How does BNST pathology interact with other brain regions in neurodegeneration?","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-f09edbae-3639-4c5d-8027-a64b95df65cd","title":"What is the temporal relationship between BNST dysfunction and cognitive decline?","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-5fed1683-cb6c-4866-a1d9-c421528d6676","title":"Does kainate receptor dysfunction precede amyloid pathology in the hippocampus?","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-9156015c-94b0-4eb9-97ef-d909ccfeb201","title":"Can AIS be protected or regenerated after injury?","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5},{"id":"open_question-8ac1d83d-d5d7-4707-ae73-5e76ef7ba846","title":"Can we target tanycytes therapeutically?","importance_elo":1500,"status":"open","potential_impact_score":0.5,"tractability_score":0.5}],"open_questions_total":20,"knowledge_gaps":[{"id":"gap-pubmed-20260410-112102-927a6a57","title":"What determines the tissue-specific role of EMP1 in ER stress regulation across different cell types?","domain":"cellular-stress-response","status":"open","importance_elo":1000.0},{"id":"gap-debate-20260410-112451-cfdde459","title":"Can lysosomal membrane stabilizers selectively prevent tau seeding without disrupting normal autophagy?","domain":"cell-biology","status":"open","importance_elo":1000.0},{"id":"gap-debate-20260410-075012-9df9e351","title":"How does membrane lipid composition quantitatively affect pathological seed uptake and propagation?","domain":"cell-biology","status":"open","importance_elo":1000.0},{"id":"gap-debate-20260410-112819-ea2b7c60","title":"How does cholesterol gradient disruption differentially affect amyloidogenic vs synaptic raft domains in human neurons?","domain":"cell-biology","status":"open","importance_elo":1000.0},{"id":"gap-debate-20260410-113038-4f6dee7d","title":"What determines the directionality and selectivity of mitochondrial transfer between specific cell types?","domain":"cell-biology","status":"open","importance_elo":1000.0},{"id":"gap-debate-20260410-100417-898d796d","title":"Do bioenergetic checkpoints (ATP/ADP ratios) causally control astrocyte subtype differentiation or merely correlate with it?","domain":"cell-biology","status":"open","importance_elo":1000.0},{"id":"gap-debate-20260410-100422-5158d7cd","title":"How do bioenergetic checkpoints (ATP/ADP ratios) mechanistically control astrocyte subtype differentiation decisions?","domain":"cellular-metabolism","status":"open","importance_elo":1000.0},{"id":"gap-human-brain-cell-types-cell-type-connectivity-frontier","title":"[landscape-frontier] Cell Type Connectivity & Electrophysiology: Human Patch-seq data is extremely scarce; most connectivity-transcriptomics linking is from mouse; in vivo functional characterization of human cell types is nearly absent.","domain":"human-brain-cell-types","status":"open","importance_elo":1000.0},{"id":"gap-debate-20260410-110247-a715bfe0","title":"Do mitochondrial-lysosome contact site defects precede or follow autophagy dysfunction in different NDDs?","domain":"cell-biology","status":"open","importance_elo":1000.0},{"id":"gap-pubmed-20260410-155331-3a6fc77a","title":"How do canonical E2Fs promote mitosis while simultaneously augmenting endocycle ploidy when ablated?","domain":"cell-biology","status":"open","importance_elo":1000.0},{"id":"gap-debate-20260410-111542-72d896bf","title":"What is the mechanistic coupling between autophagy flux and chromatin remodeling in aging neurons?","domain":"cell-biology","status":"open","importance_elo":1000.0},{"id":"gap-pubmed-20260410-165321-9459fe30","title":"How does neuroglobin simultaneously inhibit Wnt/β-catenin while enhancing NFκB activation through the same target?","domain":"cell-signaling","status":"open","importance_elo":1000.0},{"id":"gap-debate-20260410-111106-b931f830","title":"Can TFEB chronic activation cause lysosomal storage dysfunction that counteracts therapeutic benefits?","domain":"cell-biology","status":"open","importance_elo":1000.0},{"id":"gap-human-brain-cell-types-cell-type-connectivity","title":"[landscape-gap] Cell Type Connectivity & Electrophysiology: Human Patch-seq data is extremely scarce; most connectivity-transcriptomics linking is from mouse; in vivo functional characterization of human cell types is nearly absent.","domain":"human-brain-cell-types","status":"open","importance_elo":1000.0},{"id":"gap-pubmed-20260410-165659-15db1038","title":"Why does AKT1 upregulation correlate with suppressed autophagy when AKT1 typically promotes autophagy?","domain":"cellular-neurobiology","status":"open","importance_elo":1000.0},{"id":"gap-debate-20260410-112522-d365786b","title":"How does TFEB-PGC1α decoupling create selective neuronal vulnerability to protein aggregation?","domain":"cellular-biology","status":"open","importance_elo":1000.0},{"id":"gap-debate-20260410-112730-0b2fc4e8","title":"Which extracellular vesicle subtypes are the primary carriers of pathological tau between neurons?","domain":"cell-biology","status":"open","importance_elo":1000.0},{"id":"gap-pubmed-20260410-172948-b3944fd0","title":"What determines the directionality and selectivity of astrocyte-to-neuron mitochondrial transfer?","domain":"cellular-communication","status":"open","importance_elo":1000.0},{"id":"gap-pubmed-20260410-173057-0d6103ae","title":"What are the specific molecular mechanisms by which mitochondrial dysfunction disrupts osteoblast-osteoclast balance in osteoporosis?","domain":"cellular-metabolism","status":"open","importance_elo":1000.0},{"id":"gap-pubmed-20260410-180823-a961421f","title":"What molecular mechanisms link telomere dysfunction to inflammatory cytokine production in senescent endothelial cells?","domain":"cellular-senescence","status":"open","importance_elo":1000.0}],"gap_count":20,"landscape":{"id":"landscape-human-brain-cell-types-v1","title":"Human Brain Cell Type Landscape Analysis","domain":"human-brain-cell-types","created_at":"2026-04-25T18:49:06.544989-07:00"},"hypothesis_count":6,"personas":[{"id":"christof-koch","name":"Christof Koch","type":"debater","icon":"🌀","color":"#5c6bc0","debate_count":1},{"id":"rui-costa","name":"Rui Costa","type":"debater","icon":"🏃","color":"#ef5350","debate_count":1},{"id":"xiaojun-li","name":"Xiaojun Li","type":"debater","icon":"🔬","color":"#8d6e63","debate_count":0},{"id":"pete-skene","name":"Pete Skene","type":"debater","icon":"🔬","color":"#8d6e63","debate_count":0},{"id":"ed-lein","name":"Ed Lein","type":"debater","icon":"🧠","color":"#4fc3f7","debate_count":0},{"id":"clinical_trialist","name":"Clinical Trialist","type":"reviewer","icon":"📋","color":"#4dd0e1","debate_count":0},{"id":"sud-pinglay","name":"Sud Pinglay","type":"debater","icon":"🧬","color":"#26a69a","debate_count":0},{"id":"jay-shendure","name":"Jay Shendure","type":"debater","icon":"🧪","color":"#ffa726","debate_count":0},{"id":"medicinal_chemist","name":"Medicinal Chemist","type":"builder","icon":"🧪","color":"#aed581","debate_count":0}]}