RRC ID 42919
著者 Tanaka Y, Era T, Nishikawa S, Kawamata S.
タイトル Forced expression of Nanog in hematopoietic stem cells results in a gammadeltaT-cell disorder.
ジャーナル Blood
Abstract Nanog is a key molecule involved in the maintenance of the self-renewal of undifferentiated embryonic stem (ES) cells. In this work we investigate whether Nanog can enhance self-renewal in hematopoietic stem cells. Contrary to our expectation, no positive effect of Nanog transduction was detected in bone marrow reconstitution assays. However, recipients of Nanog-transduced (Nanog) hematopoietic stem cells (HSCs) invariantly develop a unique disorder typified by an atrophic thymus occupied by Nanog-expressing gammadeltaT-cell receptor-positive (TCR(+)) cells (Nanog T cells). All thymi are eventually occupied by Nanog T cells with CD25(+)CD44(+) surface phenotype that home selectively to the thymus on transfer and suppress normal thymocyte development, which is partly ascribed to destruction of the microenvironment in the thymus cortex. Moreover, this initial disorder invariantly develops to a lymphoproliferative disorder, in which Nanog T cells undergo unlimited proliferation in the peripheral lymphoid tissues and eventually kill the host. This invariable end result suggests that Nanog is a candidate oncogene for gammadeltaT-cell malignancy.
巻・号 110(1)
ページ 107-15
公開日 2007-7-1
DOI 10.1182/blood-2006-08-039628
PII S0006-4971(20)41315-1
PMID 17360937
MeSH Atrophy / genetics Bone Marrow Cells, Cultured Chemotaxis, Leukocyte DNA-Binding Proteins / genetics* DNA-Binding Proteins / pharmacology Hematopoietic Stem Cells / cytology Hematopoietic Stem Cells / metabolism* Homeodomain Proteins / genetics* Homeodomain Proteins / pharmacology Humans Hyaluronan Receptors Interleukin-2 Receptor alpha Subunit Lymphoproliferative Disorders / etiology* Lymphoproliferative Disorders / pathology Nanog Homeobox Protein Oncogenes Receptors, Antigen, T-Cell, gamma-delta* T-Lymphocytes / immunology T-Lymphocytes / pathology* Thymus Gland / physiopathology* Transduction, Genetic
IF 17.794
引用数 23
WOS 分野 HEMATOLOGY
リソース情報
ヒト・動物細胞 OP9(RCB1124)