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Ko, Myunggon
Molecular Immunology & Cancer Epigenetics
Research Interests
  • TET proteins, DNA hydroxymethylation, oncogenesis, cancer stem cells, cancer therapy


Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice

DC Field Value Language Ko, Myung Gon ko Bandukwala, Hozefa S ko An, Jungeun ko Lamperti, Edward D ko Thompson, Elizabeth C ko Hastie, Ryan ko Tsangaratou, Angeliki ko Rajewsky, Klaus ko Koralov, Sergei B ko Rao, Anjana ko 2015-07-24T06:18:27Z - 2015-07-24 ko 2011-08 ko
dc.identifier.citation PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.108, no.35, pp.14566 - 14571 ko
dc.identifier.issn 0027-8424 ko
dc.identifier.uri -
dc.description.abstract The Ten-Eleven-Translocation 2 (TET2) gene encodes a member of TET family enzymes that alters the epigenetic status of DNA by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Somatic loss-of-function mutations of TET2 are frequently observed in patients with diverse myeloid malignancies, including myelodysplastic syndromes, myeloproliferative neoplasms, and chronic myelomonocytic leukemia. By analyzing mice with targeted disruption of the Tet2 catalytic domain, we show here that Tet2 is a critical regulator of self-renewal and differentiation of hematopoietic stem cells (HSCs). Tet2 deficiency led to decreased genomic levels of 5hmC and augmented the size of the hematopoietic stem/progenitor cell pool in a cell-autonomous manner. In competitive transplantation assays, Tet2-deficient HSCs were capable of multi-lineage reconstitution and possessed a competitive advantage over wild-type HSCs, resulting in enhanced hematopoiesis into both lymphoid and myeloid lineages. In vitro, Tet2 deficiency delayed HSC differentiation and skewed development toward the monocyte/macrophage lineage. Our data indicate that Tet2 has a critical role in regulating the expansion and function of HSCs, presumably by controlling 5hmC levels at genes important for the self-renewal, proliferation, and differentiation of HSCs. ko
dc.description.statementofresponsibility close -
dc.language 영어 ko
dc.publisher NATL ACAD SCIENCES ko
dc.title Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice ko
dc.type ARTICLE ko
dc.identifier.scopusid 2-s2.0-80052284526 ko
dc.identifier.wosid 000294425900043 ko
dc.type.rims ART ko
dc.description.wostc 140 *
dc.description.scopustc 128 * 2015-12-28 * 2015-11-04 *
dc.identifier.doi 10.1073/pnas.1112317108 ko
dc.identifier.url ko
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