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

作者：Haji Yoichi; Suzuki Makiko; Moriya Kunihiko; So Takanori; Hozumi Katsuto; Mizuma Masamichi; Unno Michiaki; Ishii Naoto^*

来源：Biochemical and Biophysical Research Communications, 2014, 447(2): 346-351.

DOI：10.1016/j.bbrc.2014.04.003

• Notch]
• T cell development
• Humanized mouse

Notch] 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 Notchl (ICN1), were transplanted into severely immunodeficient NOD/Shi-scid-IL2r gamma(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 Notchl signaling in HSCs promotes CD8(+) SP T cell development, and that T cell leukemogenesis may require additional oncogenic factors other than Notchl activation.

• 出版日期2014-5-2