Component

Mouse Tet2

Mus musculus ten-eleven translocation dioxygenase 2; distinct from human protein.

10 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. Short-hairpin-RNA depletion of Tet2 in mouse haematopoietic precursors skewed their differentiation towards monocyte and macrophage lineages in culture.

    Mouse Tet2 → Monocyte and macrophage lineage skewing of mouse haematopoietic precursors source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    duration
    Culture experiment
    experimental_model
    Mouse haematopoietic precursors with shRNA knockdown, in culture
    exposure
    shRNA-mediated Tet2 depletion
    limitations
    A culture differentiation bias is not leukaemia, and knockdown is not the patient mutation.
    organism
    Mus musculus
    plain_language
    Removing Tet2 pushed young blood cells toward one lineage.
    primary_references
    [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
    tissue
    Cultured haematopoietic precursors
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    TET2 loss and malignancy: the step between a nutrient-responsive enzyme and the disease (2026-09-23) · lines 43–51

    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. · supports · Mouse haematopoietic precursors with shRNA knockdown, in culture · source_derived_draft · unverified_draft

    ## tet2-depletion-skews-mouse-precursors Short-hairpin-RNA depletion of Tet2 in mouse haematopoietic precursors skewed their differentiation towards monocyte and macrophage lineages in culture. Model/species: Mouse haematopoietic precursors with shRNA knockdown, in culture Organism: Mus musculus Tissue/system: Cultured haematopoietic precursors Exposure: shRNA-mediated Tet2 depletion Duration: Culture experiment Limits: A culture differentiation bias is not leukaemia, and knockdown is not the patient mutation. Primary 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
    Complete structured claim and evidence

  2. Inactivating Tet2 in mouse perturbed both early and late haematopoiesis in a cell-autonomous manner, gave the cells a competitive advantage, and eventually led to the development of haematological malignancies.

    Mouse Tet2 → Haematological malignancy in mice source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    duration
    In vivo, to malignancy
    experimental_model
    Tet2-inactivated mice; competitive repopulation
    exposure
    Genetic inactivation of Tet2
    limitations
    A different group from the conditional-knockout study above, but the same group as the 2009 human mutation survey in this collection, so that survey and this mouse model are one line of evidence rather than two.
    organism
    Mus musculus
    plain_language
    A second group's mice also developed blood cancers after Tet2 was switched off.
    primary_references
    [quivoron-2011] TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis (2011). https://pubmed.ncbi.nlm.nih.gov/21723201/ DOI: 10.1016/j.ccr.2011.06.003
    tissue
    Myeloid and lymphoid compartments
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    TET2 loss and malignancy: the step between a nutrient-responsive enzyme and the disease (2026-09-23) · lines 73–81

    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. · supports · Tet2-inactivated mice; competitive repopulation · source_derived_draft · unverified_draft

    ## tet2-inactivation-causes-mouse-malignancy Inactivating Tet2 in mouse perturbed both early and late haematopoiesis in a cell-autonomous manner, gave the cells a competitive advantage, and eventually led to the development of haematological malignancies. Model/species: Tet2-inactivated mice; competitive repopulation Organism: Mus musculus Tissue/system: Myeloid and lymphoid compartments Exposure: Genetic inactivation of Tet2 Duration: In vivo, to malignancy Limits: A different group from the conditional-knockout study above, but the same group as the 2009 human mutation survey in this collection, so that survey and this mouse model are one line of evidence rather than two. Primary reference: [quivoron-2011] TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis (2011). https://pubmed.ncbi.nlm.nih.gov/21723201/ DOI: 10.1016/j.ccr.2011.06.003
    Complete structured claim and evidence

  3. Conditional Tet2 loss produced progressive enlargement of the haematopoietic stem-cell compartment and eventual myeloproliferation in vivo, including splenomegaly, monocytosis and extramedullary haematopoiesis.

    Mouse Tet2 → Myeloproliferation in mice source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    duration
    Progressive, in vivo
    experimental_model
    Conditional Tet2-knockout mice followed in vivo
    exposure
    Conditional genetic deletion of Tet2
    limitations
    Myeloproliferation in a conditional knockout mouse is not the same entity as a human myelodysplastic syndrome, and this model deletes the gene rather than reproducing a point mutation.
    organism
    Mus musculus
    plain_language
    Mice without Tet2 went on to develop a blood disorder of overgrowth.
    primary_references
    [moran-crusio-2011] Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation (2011). https://pubmed.ncbi.nlm.nih.gov/21723200/ DOI: 10.1016/j.ccr.2011.06.001
    tissue
    Bone marrow, spleen and peripheral blood
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    TET2 loss and malignancy: the step between a nutrient-responsive enzyme and the disease (2026-09-23) · lines 63–71

    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. · supports · Conditional Tet2-knockout mice followed in vivo · source_derived_draft · unverified_draft

    ## tet2-loss-causes-myeloproliferation Conditional Tet2 loss produced progressive enlargement of the haematopoietic stem-cell compartment and eventual myeloproliferation in vivo, including splenomegaly, monocytosis and extramedullary haematopoiesis. Model/species: Conditional Tet2-knockout mice followed in vivo Organism: Mus musculus Tissue/system: Bone marrow, spleen and peripheral blood Exposure: Conditional genetic deletion of Tet2 Duration: Progressive, in vivo Limits: Myeloproliferation in a conditional knockout mouse is not the same entity as a human myelodysplastic syndrome, and this model deletes the gene rather than reproducing a point mutation. Primary reference: [moran-crusio-2011] Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation (2011). https://pubmed.ncbi.nlm.nih.gov/21723200/ DOI: 10.1016/j.ccr.2011.06.001
    Complete structured claim and evidence

  4. Conditional deletion of Tet2 in the mouse haematopoietic compartment increased stem-cell self-renewal in competitive transplant assays, and Tet2 heterozygous mice also showed increased self-renewal and extramedullary haematopoiesis.

    Mouse Tet2 → Mouse haematopoietic stem and progenitor cell self-renewal source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    duration
    In vivo, to the development of disease
    experimental_model
    Conditional Tet2-knockout mice; competitive transplantation
    exposure
    Conditional genetic deletion of Tet2; homozygous and heterozygous
    limitations
    Haploinsufficiency means one damaged copy already changes the phenotype; this is a genetic model, not a nutritional one.
    organism
    Mus musculus
    plain_language
    Losing Tet2 made blood stem cells renew themselves more than they should.
    primary_references
    [moran-crusio-2011] Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation (2011). https://pubmed.ncbi.nlm.nih.gov/21723200/ DOI: 10.1016/j.ccr.2011.06.001
    tissue
    Haematopoietic stem cell compartment
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    TET2 loss and malignancy: the step between a nutrient-responsive enzyme and the disease (2026-09-23) · lines 53–61

    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. · supports · Conditional Tet2-knockout mice; competitive transplantation · source_derived_draft · unverified_draft

    ## tet2-loss-increases-hspc-self-renewal Conditional deletion of Tet2 in the mouse haematopoietic compartment increased stem-cell self-renewal in competitive transplant assays, and Tet2 heterozygous mice also showed increased self-renewal and extramedullary haematopoiesis. Model/species: Conditional Tet2-knockout mice; competitive transplantation Organism: Mus musculus Tissue/system: Haematopoietic stem cell compartment Exposure: Conditional genetic deletion of Tet2; homozygous and heterozygous Duration: In vivo, to the development of disease Limits: Haploinsufficiency means one damaged copy already changes the phenotype; this is a genetic model, not a nutritional one. Primary reference: [moran-crusio-2011] Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation (2011). https://pubmed.ncbi.nlm.nih.gov/21723200/ DOI: 10.1016/j.ccr.2011.06.001
    Complete structured claim and evidence

  5. 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.

    Mouse Tet2 → Mouse haematopoietic stem and progenitor cell self-renewal source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    duration
    In vitro and in vivo after restoration
    experimental_model
    Reversible transgenic RNAi mouse permitting Tet2 knockdown and restoration
    exposure
    Genetic restoration of endogenous Tet2 expression after knockdown
    limitations
    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.
    organism
    Mus musculus
    plain_language
    Switching Tet2 back on undid the abnormal renewal, which is the strongest sign the enzyme itself was responsible.
    primary_references
    [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
    tissue
    Haematopoietic stem and progenitor cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    TET2 loss and malignancy: the step between a nutrient-responsive enzyme and the disease (2026-09-23) · lines 93–101

    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. · supports · Reversible transgenic RNAi mouse permitting Tet2 knockdown and restoration · source_derived_draft · unverified_draft

    ## tet2-restoration-reverses-self-renewal 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. Model/species: Reversible transgenic RNAi mouse permitting Tet2 knockdown and restoration Organism: Mus musculus Tissue/system: Haematopoietic stem and progenitor cells Exposure: Genetic restoration of endogenous Tet2 expression after knockdown Duration: In vitro and in vivo after restoration Limits: 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. Primary 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
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. 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.

    L-Ascorbate → Mouse haematopoietic stem cell frequency source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    duration
    Systemic depletion in vivo
    experimental_model
    Mice under systemic ascorbate depletion; metabolomics of rare cell populations isolated directly from tissues
    exposure
    Systemic ascorbate depletion; the retrieved abstract does not state the strain or the depletion protocol
    limitations
    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.
    organism
    Mus musculus
    plain_language
    Taking vitamin C away made blood stem cells multiply more, partly by slowing the enzyme.
    primary_references
    [agathocleous-2017] Ascorbate regulates haematopoietic stem cell function and leukaemogenesis (2017). https://pubmed.ncbi.nlm.nih.gov/28825709/ DOI: 10.1038/nature23876
    tissue
    Haematopoietic stem cells
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    TET2 loss and malignancy: the step between a nutrient-responsive enzyme and the disease (2026-09-23) · lines 123–131

    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. · supports · Mice under systemic ascorbate depletion; metabolomics of rare cell populations isolated directly from tissues · source_derived_draft · unverified_draft

    ## ascorbate-depletion-raises-hsc-frequency 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. Model/species: Mice under systemic ascorbate depletion; metabolomics of rare cell populations isolated directly from tissues Organism: Mus musculus Tissue/system: Haematopoietic stem cells Exposure: Systemic ascorbate depletion; the retrieved abstract does not state the strain or the depletion protocol Duration: Systemic depletion in vivo Limits: 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. Primary reference: [agathocleous-2017] Ascorbate regulates haematopoietic stem cell function and leukaemogenesis (2017). https://pubmed.ncbi.nlm.nih.gov/28825709/ DOI: 10.1038/nature23876
    Complete structured claim and evidence

  2. Vitamin C treatment enhanced 5-hydroxymethylcytosine formation in Tet2-deficient mouse haematopoietic stem and progenitor cells, mimicking genetic Tet2 restoration.

    L-Ascorbate → DNA 5-hydroxymethylcytosine residues source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    duration
    Treatment in culture and in vivo
    experimental_model
    Tet2-deficient mouse haematopoietic stem and progenitor cells
    exposure
    Vitamin C as a cofactor of Fe(II)- and 2-oxoglutarate-dependent dioxygenases
    limitations
    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.
    organism
    Mus musculus
    plain_language
    Vitamin C raised the same chemical mark that restoring the enzyme raises.
    primary_references
    [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
    tissue
    Haematopoietic stem and progenitor cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    TET2 loss and malignancy: the step between a nutrient-responsive enzyme and the disease (2026-09-23) · lines 103–111

    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. · supports · Tet2-deficient mouse haematopoietic stem and progenitor cells · source_derived_draft · unverified_draft

    ## ascorbate-raises-5hmc-in-tet2-deficient-hspc Vitamin C treatment enhanced 5-hydroxymethylcytosine formation in Tet2-deficient mouse haematopoietic stem and progenitor cells, mimicking genetic Tet2 restoration. Model/species: Tet2-deficient mouse haematopoietic stem and progenitor cells Organism: Mus musculus Tissue/system: Haematopoietic stem and progenitor cells Exposure: Vitamin C as a cofactor of Fe(II)- and 2-oxoglutarate-dependent dioxygenases Duration: Treatment in culture and in vivo Limits: 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. Primary 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
    Complete structured claim and evidence

  3. Adding L-ascorbic acid 2-phosphate to mouse ESC medium rapidly increased global DNA 5hmC and promoter-associated 5hmC, preceding later methylcytosine loss.

    L-Ascorbic acid 2-phosphate → DNA 5-hydroxymethylcytosine residues source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Figures 1–2
    experimental_model
    Mouse Oct4-GiP ESCs in feeder-free 2i/LIF medium; DNA dot blot and hydroxymethyl-DNA immunoprecipitation
    exposure
    100 µg/mL L-ascorbic acid 2-phosphate (A8960), medium replaced daily; 12-h and 72-h sampling.
    limitations
    5hmC abundance alone is not proof of completed demethylation; cultured ESCs are not adult human tissues.
    nutrient_topic
    Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
    organism
    Mus musculus
    plain_language
    A stable vitamin C derivative increased an early DNA-demethylation intermediate in cultured mouse stem cells.
    primary_references
    [c-reg-blaschke] Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23812591/ DOI: 10.1038/nature12362
    tissue_or_cell_type
    Embryonic stem cells

    Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 977–989

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse Oct4-GiP ESCs in feeder-free 2i/LIF medium; DNA dot blot and hydroxymethyl-DNA immunoprecipitation · source_derived_draft · unverified_draft

    ### c-reg-esc-hydroxymethylation Adding L-ascorbic acid 2-phosphate to mouse ESC medium rapidly increased global DNA 5hmC and promoter-associated 5hmC, preceding later methylcytosine loss. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: A stable vitamin C derivative increased an early DNA-demethylation intermediate in cultured mouse stem cells. organism: Mus musculus tissue_or_cell_type: Embryonic stem cells experimental_model: Mouse Oct4-GiP ESCs in feeder-free 2i/LIF medium; DNA dot blot and hydroxymethyl-DNA immunoprecipitation limitations: 5hmC abundance alone is not proof of completed demethylation; cultured ESCs are not adult human tissues. exposure: 100 µg/mL L-ascorbic acid 2-phosphate (A8960), medium replaced daily; 12-h and 72-h sampling. cross_nutrient: false evidence_location: Figures 1–2 [c-reg-blaschke] Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23812591/ DOI: 10.1038/nature12362
    Complete structured claim and evidence

  4. After vitamin C derivative treatment, numerous mouse ESC promoters lost methylcytosine; imprinted regions and IAP retroelements were relatively resistant, so the effect was not indiscriminate erasure of genomic methylation.

    L-Ascorbic acid 2-phosphate → Gene-promoter DNA methylation source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Figure 2; resistant-region analysis
    experimental_model
    Mouse Oct4-GiP ESCs in feeder-free 2i/LIF medium; DNA dot blot and hydroxymethyl-DNA immunoprecipitation; mC-DIP sequencing/qPCR and bisulfite validation
    exposure
    100 µg/mL L-ascorbic acid 2-phosphate (A8960), medium replaced daily; 12-h and 72-h sampling.
    limitations
    Locus-selective cell-culture result; promoter demethylation did not automatically activate every affected gene.
    nutrient_topic
    Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
    organism
    Mus musculus
    plain_language
    Vitamin C changed selected DNA methylation patterns in these cells; protected regions retained their marks.
    primary_references
    [c-reg-blaschke] Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23812591/ DOI: 10.1038/nature12362
    tissue_or_cell_type
    Embryonic stem cells

    Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 991–1003

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse Oct4-GiP ESCs in feeder-free 2i/LIF medium; DNA dot blot and hydroxymethyl-DNA immunoprecipitation; mC-DIP sequencing/qPCR and bisulfite validation · source_derived_draft · unverified_draft

    ### c-reg-esc-promoter-demethylation After vitamin C derivative treatment, numerous mouse ESC promoters lost methylcytosine; imprinted regions and IAP retroelements were relatively resistant, so the effect was not indiscriminate erasure of genomic methylation. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C changed selected DNA methylation patterns in these cells; protected regions retained their marks. organism: Mus musculus tissue_or_cell_type: Embryonic stem cells experimental_model: Mouse Oct4-GiP ESCs in feeder-free 2i/LIF medium; DNA dot blot and hydroxymethyl-DNA immunoprecipitation; mC-DIP sequencing/qPCR and bisulfite validation limitations: Locus-selective cell-culture result; promoter demethylation did not automatically activate every affected gene. exposure: 100 µg/mL L-ascorbic acid 2-phosphate (A8960), medium replaced daily; 12-h and 72-h sampling. cross_nutrient: false evidence_location: Figure 2; resistant-region analysis [c-reg-blaschke] Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23812591/ DOI: 10.1038/nature12362
    Complete structured claim and evidence

  5. Ascorbate co-treatment increased Oct4:GFP-positive colony formation during KLF4-driven mouse EpiSC reprogramming and shifted the optimum toward lower retinol concentration; higher retinol suppressed colony formation rather than improving it indefinitely.

    L-Ascorbate → Reprogramming to induced pluripotency source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    evidence_location
    Figure 4A–C
    experimental_model
    KLF4-expressing OEC-2 mouse EpiSCs switched to vitamin-A-free 2i/LIF; Oct4:GFP colony counts
    exposure
    50 µg/mL ascorbate with 0–50 ng/mL retinol; day-6 colony endpoint; combined optimum reported near 3.13 ng/mL retinol.
    limitations
    Reprogramming reporter assay, not demonstrated tissue rejuvenation or therapy; relationship to DNA modification is supported by complementary experiments, not sole-cause proof.
    nutrient_topic
    Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
    organism
    Mus musculus
    plain_language
    Vitamin A and C worked together in this stem-cell culture protocol, but more vitamin A was not always better.
    primary_references
    [c-reg-hore] Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms. (2016). https://pubmed.ncbi.nlm.nih.gov/27729528/ DOI: 10.1073/pnas.1608679113
    tissue_or_cell_type
    Epiblast stem-cell culture

    Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1075–1087

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · KLF4-expressing OEC-2 mouse EpiSCs switched to vitamin-A-free 2i/LIF; Oct4:GFP colony counts · source_derived_draft · unverified_draft

    ### c-reg-retinol-ascorbate-reprogramming Ascorbate co-treatment increased Oct4:GFP-positive colony formation during KLF4-driven mouse EpiSC reprogramming and shifted the optimum toward lower retinol concentration; higher retinol suppressed colony formation rather than improving it indefinitely. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin A and C worked together in this stem-cell culture protocol, but more vitamin A was not always better. organism: Mus musculus tissue_or_cell_type: Epiblast stem-cell culture experimental_model: KLF4-expressing OEC-2 mouse EpiSCs switched to vitamin-A-free 2i/LIF; Oct4:GFP colony counts limitations: Reprogramming reporter assay, not demonstrated tissue rejuvenation or therapy; relationship to DNA modification is supported by complementary experiments, not sole-cause proof. exposure: 50 µg/mL ascorbate with 0–50 ng/mL retinol; day-6 colony endpoint; combined optimum reported near 3.13 ng/mL retinol. cross_nutrient: true evidence_location: Figure 4A–C [c-reg-hore] Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms. (2016). https://pubmed.ncbi.nlm.nih.gov/27729528/ DOI: 10.1073/pnas.1608679113
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards