RRC ID 36658
Author Haji Y, Suzuki M, Moriya K, So T, Hozumi K, Mizuma M, Unno M, Ishii N.
Title Activation of Notch1 promotes development of human CD8(+) single positive T cells in humanized mice.
Journal 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.
Volume 447(2)
Pages 346-51
Published 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 2.559
Times Cited 2
WOS Category BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Cord blood stem cells for research 研究用ヒト臍帯血幹細胞