Activation of Notch1 promotes development of human CD8+ single positive T cells in humanized mice

Yoichi Haji, Makiko Suzuki, Kunihiko Moriya, Takanori So, Katsuto Hozumi, Masamichi Mizuma, Michiaki Unno, Naoto Ishii

研究成果: Article査読

6 被引用数 (Scopus)


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-IL2rγnull (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.

ジャーナルBiochemical and biophysical research communications
出版ステータスPublished - 2014 5 2

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学


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