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Development of murine models for the functional study of normal stem cells and cancer cells and the comparative transcriptome and proteome analysis of those cells and their progeny

Grant number: 09/54218-1
Support type:Multi-user Equipment Program
Duration: October 01, 2010 - September 30, 2012
Field of knowledge:Health Sciences - Medicine
Principal researcher:Eduardo Magalhães Rego
Grantee:Eduardo Magalhães Rego
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
As informações de acesso ao Equipamento Multiusuário são de responsabilidade do Pesquisador responsável
EMU web page: Página do Equipamento Multiusuário não informada
Type of equipment: Tipo de Equipamento Multiusuário não informado
Manufacturer: Fabricante não informado
Model: Modelo não informado


Because of their similarity to hematopoietic stem cells (HSCs), the immature progenitor cells seen in malignant tumors and the various forms of leukemia have been designated cancer stem cells (CSCs). The CSCs are capable of dividing asymmetrically, giving rise to tumor cells that are more differentiated or to identical daughter cells. Because they can repopulate the tumor after chemotherapy, CSCs are responsible for the maintenance/recurrence of the disease. In addition, CSCs are quiescent and are therefore inherently resistant to the effects of the drugs conventionally used in cancer therapy. The identification of CSCs is based on functional tests, the most common model being transplantation of cells into immunodeficient mice. Although it has been demonstrated that CSCs are present in various malignancies, the nature of these cells remains largely unknown. The objective of this proposal is to combine in vivo assays (using immunodeficient, genetically manipulated, or lethally irradiated animals) with methods of transcriptome and proteome analysis for the study of various stem cells. Five major projects (comprising more than 30 subprojects) will be developed: a) using murine models to identify subpopulation of cells with CSC characteristics in leukemia associated with the hybrid proteins CALM-AF10 and PML-RARA; b) identification of signaling pathways presenting aberrant activity in CSCs and their progeny in acute leukemia and breast cancer; c) analysis of the effect of topotecan blockade of the HIF-1a gene in glioblastoma multiforme cell lines—in vitro and in mice with combined immunodeficiency after exposure to ionizing radiation; d) study of HSCs and hematopoietic precursors in a mouse model of dyskeratosis congenita (altered ribosomal function and a propensity to develop cancer); e) determination of regenerative efficiency of induced pluripotent stem cells, using retroviral vectors, in animal models; and f) identification of the pathways involved in the differentiation, quiescence and apoptosis of induced pluripotent stem cells. (AU)

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