{"id":"4248ff21-d172-5f83-ada9-30cb0c254fb1","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:tet2-depletion-skews-mouse-precursors","predicate":"knockdown_increases","statement":"Short-hairpin-RNA depletion of Tet2 in mouse haematopoietic precursors skewed their differentiation towards monocyte and macrophage lineages in culture.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"10d14e24-e755-54f2-a9a1-764dc72a1233","mechanism_event_label":"Short-hairpin-RNA depletion of Tet2 in mouse haematopoietic precursors skewed their differentiation towards monocyte and macrophage lineages in culture.","subject":{"id":"36d7160b-6534-58a6-a0df-55bcde8e740c","slug":"tet2-mouse","display_name":"Mouse Tet2","entity_type_key":"protein"},"object":{"id":"2bdbb3eb-1b9c-5826-a88e-b843b55935eb","slug":"mouse-monocyte-macrophage-skewing","display_name":"Monocyte and macrophage lineage skewing of mouse haematopoietic precursors","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"10d14e24-e755-54f2-a9a1-764dc72a1233","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:tet2-depletion-skews-mouse-precursors-event","event_type":"observed_relationship","label":"Short-hairpin-RNA depletion of Tet2 in mouse haematopoietic precursors skewed their differentiation towards monocyte and macrophage lineages in culture.","description":"Removing Tet2 pushed young blood cells toward one lineage.","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":"2bdbb3eb-1b9c-5826-a88e-b843b55935eb","slug":"mouse-monocyte-macrophage-skewing","display_name":"Monocyte and macrophage lineage skewing of mouse haematopoietic precursors","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":"Culture experiment","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse haematopoietic precursors with shRNA knockdown, in culture","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"shRNA-mediated Tet2 depletion","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A culture differentiation bias is not leukaemia, and knockdown is not the patient mutation.","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":"Removing Tet2 pushed young blood cells toward one lineage.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ko-2010] Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2 (2010). https://pubmed.ncbi.nlm.nih.gov/21057493/ DOI: 10.1038/nature09586","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Cultured haematopoietic precursors","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":"0c34cff1-0b0c-5c42-8ccd-1fe4f2ba7b42","evidence_kind":"source_excerpt","locator":"Lines 43-51","start_line":43,"end_line":51,"excerpt":"## tet2-depletion-skews-mouse-precursors\nShort-hairpin-RNA depletion of Tet2 in mouse haematopoietic precursors skewed their differentiation towards monocyte and macrophage lineages in culture.\nModel/species: Mouse haematopoietic precursors with shRNA knockdown, in culture\nOrganism: Mus musculus\nTissue/system: Cultured haematopoietic precursors\nExposure: shRNA-mediated Tet2 depletion\nDuration: Culture experiment\nLimits: A culture differentiation bias is not leukaemia, and knockdown is not the patient mutation.\nPrimary reference: [ko-2010] Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2 (2010). https://pubmed.ncbi.nlm.nih.gov/21057493/ DOI: 10.1038/nature09586","model_system":"Mouse haematopoietic precursors with shRNA knockdown, in culture","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}