Enhanced Neural Progenitor/Stem Cells Self-Renewal via the Interaction of Stress-Inducible Protein 1 with the Prion Protein

Autor(es)

Santos, Tiago G. ^{[1, 2]} ; Silva, Iara R. ^{[1, 2]} ; Costa-Silva, Bruno ^{[1, 2]} ; Lepique, Ana Paula ^[3] ; Martins, Vilma R. ^{[1, 2]} ; Lopes, Marilene H. ^{[4, 5]}

Afiliação do(s) autor(es)

^[1] AC Camargo Hosp, Antonio Prudente Fdn, Int Ctr Res & Educ, Dept Mol & Cell Biol, Sao Paulo - Brazil

^[2] Natl Inst Translat Neurosci CNPq MCT, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, BR-05508900 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Dept Cell & Dev Biol, Inst Biomed Sci, BR-05508900 Sao Paulo - Brazil

^[5] Hosp Alemao Oswaldo Cruz, Ludwig Inst Canc Res, Lab Mol & Cell Biol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Stem Cells; v. 29, n. 7, p. 1126-1136, JUL 2011.
• Citações Web of Science: 39

Resumo

Prion protein (PrPC), when associated with the secreted form of the stress-inducible protein 1 (STI1), plays an important role in neural survival, neuritogenesis, and memory formation. However, the role of the PrP(C)-STI1 complex in the physiology of neural progenitor/stem cells is unknown. In this article, we observed that neurospheres cultured from fetal forebrain of wild-type (Prnp(+/+)) and PrP(C)-null (Prnp(0/0)) mice were maintained for several passages without the loss of self-renewal or multipotentiality, as assessed by their continued capacity to generate neurons, astrocytes, and oligodendrocytes. The homogeneous expression and colocalization of STI1 and PrP(C) suggest that they may associate and function as a complex in neurosphere-derived stem cells. The formation of neurospheres from Prnp(0/0) mice was reduced significantly when compared with their wild-type counterparts. In addition, blockade of secreted STI1, and its cell surface ligand, PrP(C), with specific antibodies, impaired Prnp(+/+) neurosphere formation without further impairing the formation of Prnp(0/0) neurospheres. Alternatively, neurosphere formation was enhanced by recombinant STI1 application in cells expressing PrP(C) but not in cells from Prnp(0/0) mice. The STI1-PrP(C) interaction was able to stimulate cell proliferation in the neurosphere-forming assay, while no effect on cell survival or the expression of neural markers was observed. These data suggest that the STI1-PrP(C) complex may play a critical role in neural progenitor/stem cells self-renewal via the modulation of cell proliferation, leading to the control of the stemness capacity of these cells during nervous system development. STEM CELLS 2011;29:1126-1136 (AU)

• Processo FAPESP: 03/13189-2 - Papel da proteína prion celular em processos fisiológicos e patológicos II
• Beneficiário: Vilma Regina Martins
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 07/08410-2 - Papel da interação STI1-PrPc na biologia de células tronco nos contextos fisiológico e neoplásico
• Beneficiário: Marilene Hohmuth Lopes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/14027-2 - Mecanismos associados à função da proteína prion e seu ligante STI1/Hop: abordagens terapêuticas
• Beneficiário: Vilma Regina Martins
• Modalidade de apoio: Auxílio à Pesquisa - Temático