{"id":"00b47cc0-f2e5-5bbb-b3df-d4e8e86f85bf","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:tet2-restoration-reverses-self-renewal","predicate":"restoration_reduces","statement":"Restoring endogenous Tet2 expression in a reversible transgenic RNAi mouse reversed aberrant haematopoietic stem and progenitor cell self-renewal both in vitro and in vivo.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"b19886eb-0057-55f7-9290-b04a9240503a","mechanism_event_label":"Restoring endogenous Tet2 expression in a reversible transgenic RNAi mouse reversed aberrant haematopoietic stem and progenitor cell self-renewal both in vitro and in vivo.","subject":{"id":"36d7160b-6534-58a6-a0df-55bcde8e740c","slug":"tet2-mouse","display_name":"Mouse Tet2","entity_type_key":"protein"},"object":{"id":"ff7cb8a3-f953-5748-9d92-def3acf2ba95","slug":"mouse-hspc-self-renewal","display_name":"Mouse haematopoietic stem and progenitor cell self-renewal","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"b19886eb-0057-55f7-9290-b04a9240503a","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:tet2-restoration-reverses-self-renewal-event","event_type":"observed_relationship","label":"Restoring endogenous Tet2 expression in a reversible transgenic RNAi mouse reversed aberrant haematopoietic stem and progenitor cell self-renewal both in vitro and in vivo.","description":"Switching Tet2 back on undid the abnormal renewal, which is the strongest sign the enzyme itself was responsible.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"36d7160b-6534-58a6-a0df-55bcde8e740c","slug":"tet2-mouse","display_name":"Mouse Tet2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ff7cb8a3-f953-5748-9d92-def3acf2ba95","slug":"mouse-hspc-self-renewal","display_name":"Mouse haematopoietic stem and progenitor cell self-renewal","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"duration","value_text":"In vitro and in vivo after restoration","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Reversible transgenic RNAi mouse permitting Tet2 knockdown and restoration","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Genetic restoration of endogenous Tet2 expression after knockdown","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Restoring a knockdown is not the same as correcting a mutated allele in a patient, and the reversal was measured as self-renewal rather than as cure of an established leukaemia.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Switching Tet2 back on undid the abnormal renewal, which is the strongest sign the enzyme itself was responsible.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[cimmino-2017] Restoration of TET2 function blocks aberrant self-renewal and leukemia progression (2017). https://pubmed.ncbi.nlm.nih.gov/28823558/ DOI: 10.1016/j.cell.2017.07.032","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Haematopoietic stem and progenitor cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"e55fac2b-b525-522b-9498-742070b0912b","evidence_kind":"source_excerpt","locator":"Lines 93-101","start_line":93,"end_line":101,"excerpt":"## tet2-restoration-reverses-self-renewal\nRestoring endogenous Tet2 expression in a reversible transgenic RNAi mouse reversed aberrant haematopoietic stem and progenitor cell self-renewal both in vitro and in vivo.\nModel/species: Reversible transgenic RNAi mouse permitting Tet2 knockdown and restoration\nOrganism: Mus musculus\nTissue/system: Haematopoietic stem and progenitor cells\nExposure: Genetic restoration of endogenous Tet2 expression after knockdown\nDuration: In vitro and in vivo after restoration\nLimits: Restoring a knockdown is not the same as correcting a mutated allele in a patient, and the reversal was measured as self-renewal rather than as cure of an established leukaemia.\nPrimary reference: [cimmino-2017] Restoration of TET2 function blocks aberrant self-renewal and leukemia progression (2017). https://pubmed.ncbi.nlm.nih.gov/28823558/ DOI: 10.1016/j.cell.2017.07.032","model_system":"Reversible transgenic RNAi mouse permitting Tet2 knockdown and restoration","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c0b9b176-985b-55c7-b8f5-f3ca16a7ddfe","stable_key":"import-a2968a2f-5b00-5212-8b8c-8a4262bcb149","title":"TET2 loss and malignancy: the step between a nutrient-responsive enzyme and the disease (2026-09-23)","document_type":"imported_text","citation_label":"Original AI-assisted curation of twelve primary studies located by Europe PMC title search, with every statement drafted from the retrieved abstract. Two pairs share a laboratory and are recorded as one line of evidence each. Genetic loss of function, pharmacological exposure and dietary depletion are kept as separate record types. Not publisher full text.","file_path":"","sha256":"22e2c8388d4f0c1813546ba6a9ccee3fa14c0c8f578bd9bd80103c1390b2536b","revision_id":"fbc29d8d-0420-562c-bfdb-1b5af42f2d08","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}