{"id":"d51bdf18-d01f-5733-bdbc-44c02efe8493","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:ascorbate-depletion-raises-hsc-frequency","predicate":"depletion_increases","statement":"Systemic ascorbate depletion in mice increased haematopoietic stem cell frequency and function, in part by reducing the function of Tet2, and haematopoietic stem cells were shown to hold unusually high ascorbate that falls with differentiation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"da52ff74-de86-53d6-9c58-3917cd62246a","mechanism_event_label":"Systemic ascorbate depletion in mice increased haematopoietic stem cell frequency and function, in part by reducing the function of Tet2, and haematopoietic stem cells were shown to hold unusually high ascorbate that falls with differentiation.","subject":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"object":{"id":"0d79a7b8-6a30-58fc-b6b6-c308b55c3b8b","slug":"mouse-hsc-frequency","display_name":"Mouse haematopoietic stem cell frequency","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"da52ff74-de86-53d6-9c58-3917cd62246a","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:ascorbate-depletion-raises-hsc-frequency-event","event_type":"observed_relationship","label":"Systemic ascorbate depletion in mice increased haematopoietic stem cell frequency and function, in part by reducing the function of Tet2, and haematopoietic stem cells were shown to hold unusually high ascorbate that falls with differentiation.","description":"Taking vitamin C away made blood stem cells multiply more, partly by slowing the enzyme.","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":"0d79a7b8-6a30-58fc-b6b6-c308b55c3b8b","slug":"mouse-hsc-frequency","display_name":"Mouse haematopoietic stem cell frequency","entity_type_key":"cellular_process"},"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 partly mediating the effect","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"duration","value_text":"Systemic depletion in vivo","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mice under systemic ascorbate depletion; metabolomics of rare cell populations isolated directly from tissues","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Systemic ascorbate depletion; the retrieved abstract does not state the strain or the depletion protocol","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The retrieved abstract does not state the strain or protocol used to deplete ascorbate. Mice ordinarily synthesise their own ascorbate, so a mouse depletion model is not equivalent to human dietary deficiency, and more stem cells is not by itself a disease.","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":"Taking vitamin C away made blood stem cells multiply more, partly by slowing the enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[agathocleous-2017] Ascorbate regulates haematopoietic stem cell function and leukaemogenesis (2017). https://pubmed.ncbi.nlm.nih.gov/28825709/ DOI: 10.1038/nature23876","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Haematopoietic stem cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"d9ddff80-0a16-5bb7-b46d-c1e9c1954bd0","evidence_kind":"source_excerpt","locator":"Lines 123-131","start_line":123,"end_line":131,"excerpt":"## ascorbate-depletion-raises-hsc-frequency\nSystemic ascorbate depletion in mice increased haematopoietic stem cell frequency and function, in part by reducing the function of Tet2, and haematopoietic stem cells were shown to hold unusually high ascorbate that falls with differentiation.\nModel/species: Mice under systemic ascorbate depletion; metabolomics of rare cell populations isolated directly from tissues\nOrganism: Mus musculus\nTissue/system: Haematopoietic stem cells\nExposure: Systemic ascorbate depletion; the retrieved abstract does not state the strain or the depletion protocol\nDuration: Systemic depletion in vivo\nLimits: The retrieved abstract does not state the strain or protocol used to deplete ascorbate. Mice ordinarily synthesise their own ascorbate, so a mouse depletion model is not equivalent to human dietary deficiency, and more stem cells is not by itself a disease.\nPrimary reference: [agathocleous-2017] Ascorbate regulates haematopoietic stem cell function and leukaemogenesis (2017). https://pubmed.ncbi.nlm.nih.gov/28825709/ DOI: 10.1038/nature23876","model_system":"Mice under systemic ascorbate depletion; metabolomics of rare cell populations isolated directly from tissues","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}