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

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

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-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.

Original languageEnglish
Pages (from-to)346-351
Number of pages6
JournalBiochemical and biophysical research communications
Volume447
Issue number2
DOIs
Publication statusPublished - 2014 May 2

Keywords

  • Humanized mouse
  • Notch1
  • T cell development

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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