RRC ID |
36658
|
著者 |
Haji Y, Suzuki M, Moriya K, So T, Hozumi K, Mizuma M, Unno M, Ishii N.
|
タイトル |
Activation of Notch1 promotes development of human CD8(+) single positive T cells in humanized mice.
|
ジャーナル |
Biochem Biophys Res Commun
|
Abstract |
Notch1 mutations are found in more than 50% of human T cell acute lymphoblastic leukemia (T-ALL) cells. However, the functions of Notch1 for human T cell development and leukemogenesis are not well understood. To examine the role of Notch1, human hematopoietic stem cells (HSCs), which had been transduced with a constitutively active form of Notch1 (ICN1), were transplanted into severely immunodeficient NOD/Shi-scid-IL2rγ(null) (NOG) mice. We found that the great majority of the ICN1-expressing hematopoietic cells in the bone marrow expressed surface markers for T cells, such as CD3, CD4, and CD8, and that this T cell development was independent of the thymus. Accordingly, phenotypically mature CD8(+) single positive (SP) T cells were observed in the spleen. Furthermore, T-ALL developed in one NOG recipient mouse out of 26 that had been secondary transferred with the T cells developed in the first NOG mice. These results indicate that Notch1 signaling in HSCs promotes CD8(+) SP T cell development, and that T cell leukemogenesis may require additional oncogenic factors other than Notch1 activation.
|
巻・号 |
447(2)
|
ページ |
346-51
|
公開日 |
2014-5-2
|
DOI |
10.1016/j.bbrc.2014.04.003
|
PII |
S0006-291X(14)00634-2
|
PMID |
24726647
|
MeSH |
Animals
CD8-Positive T-Lymphocytes / metabolism
CD8-Positive T-Lymphocytes / pathology*
Carcinogenesis*
Disease Models, Animal
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells / metabolism
Hematopoietic Stem Cells / pathology*
Humans
Mice
Mice, Inbred NOD
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology*
Receptor, Notch1 / genetics
Receptor, Notch1 / metabolism*
Spleen / pathology
|
IF |
2.985
|
引用数 |
4
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
研究用ヒト臍帯血幹細胞 |
研究用ヒト臍帯血幹細胞 |