{"id":"c5751795-a8d2-5d2e-8b14-c9a92e232c66","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:ascorbate-raises-5hmc-in-tet2-deficient-hspc","predicate":"increases","statement":"Vitamin C treatment enhanced 5-hydroxymethylcytosine formation in Tet2-deficient mouse haematopoietic stem and progenitor cells, mimicking genetic Tet2 restoration.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"fcd42338-b53f-577c-af7a-b9836063dc10","mechanism_event_label":"Vitamin C treatment enhanced 5-hydroxymethylcytosine formation in Tet2-deficient mouse haematopoietic stem and progenitor cells, mimicking genetic Tet2 restoration.","subject":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"object":{"id":"befcc80f-1af7-53f5-b162-4eefaafc4cf0","slug":"dna-5-hydroxymethylcytosine","display_name":"DNA 5-hydroxymethylcytosine residues","entity_type_key":"chemical_species"},"evidence_count":1,"mechanism_event":{"id":"fcd42338-b53f-577c-af7a-b9836063dc10","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:ascorbate-raises-5hmc-in-tet2-deficient-hspc-event","event_type":"observed_relationship","label":"Vitamin C treatment enhanced 5-hydroxymethylcytosine formation in Tet2-deficient mouse haematopoietic stem and progenitor cells, mimicking genetic Tet2 restoration.","description":"Vitamin C raised the same chemical mark that restoring the enzyme raises.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"befcc80f-1af7-53f5-b162-4eefaafc4cf0","slug":"dna-5-hydroxymethylcytosine","display_name":"DNA 5-hydroxymethylcytosine residues","entity_type_key":"chemical_species"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"36d7160b-6534-58a6-a0df-55bcde8e740c","slug":"tet2-mouse","display_name":"Mouse Tet2","entity_type_key":"protein"},"role":"enzyme the treatment acts through","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"duration","value_text":"Treatment in culture and in vivo","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Tet2-deficient mouse haematopoietic stem and progenitor cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Vitamin C as a cofactor of Fe(II)- and 2-oxoglutarate-dependent dioxygenases","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Vitamin C is a cofactor for the whole family of Fe(II)- and 2-oxoglutarate-dependent dioxygenases, so raised 5hmC in a Tet2-deficient cell does not establish that TET2 itself was reactivated.","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":"Vitamin C raised the same chemical mark that restoring the enzyme raises.","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":"7dff349c-a57b-5e3f-9922-6b228f1d1216","evidence_kind":"source_excerpt","locator":"Lines 103-111","start_line":103,"end_line":111,"excerpt":"## ascorbate-raises-5hmc-in-tet2-deficient-hspc\nVitamin C treatment enhanced 5-hydroxymethylcytosine formation in Tet2-deficient mouse haematopoietic stem and progenitor cells, mimicking genetic Tet2 restoration.\nModel/species: Tet2-deficient mouse haematopoietic stem and progenitor cells\nOrganism: Mus musculus\nTissue/system: Haematopoietic stem and progenitor cells\nExposure: Vitamin C as a cofactor of Fe(II)- and 2-oxoglutarate-dependent dioxygenases\nDuration: Treatment in culture and in vivo\nLimits: Vitamin C is a cofactor for the whole family of Fe(II)- and 2-oxoglutarate-dependent dioxygenases, so raised 5hmC in a Tet2-deficient cell does not establish that TET2 itself was reactivated.\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":"Tet2-deficient mouse haematopoietic stem and progenitor cells","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}