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Tissue-Specific Stem Cells
Article first published online: 29 JUN 2011
Copyright © 2011 AlphaMed Press
Volume 29, Issue 7, pages 1126–1136, July 2011
How to Cite
Santos, T. G., Silva, I. R., Costa-Silva, B., Lepique, A. P., Martins, V. R. and Lopes, M. H. (2011), Enhanced Neural Progenitor/Stem Cells Self-Renewal via the Interaction of Stress-Inducible Protein 1 with the Prion Protein. STEM CELLS, 29: 1126–1136. doi: 10.1002/stem.664
Author contributions: T.G.S.: conception and design, collection and assembly of data and manuscript writing; I.R.S. and B.C.S.: collection and/or assembly of data; A.P.L.: data analysis and interpretation; V.R.M.: data analysis and interpretation, manuscript writing, final approval of manuscript; M.H.L.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS May 23, 2011.
- Issue published online: 29 JUN 2011
- Article first published online: 29 JUN 2011
- Accepted manuscript online: 23 MAY 2011 10:31AM EST
- Manuscript Accepted: 2 MAY 2011
- Manuscript Received: 23 DEC 2010
- Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP. Grant Numbers: 07/08410-2, 09/14027-2, 03/13189-2
- Programa Institutos Nacionais de Ciência e Tecnologia
- do Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq/MCT)
- Ludwig Institute for Cancer Research
- Prion protein;
- Stress inducible protein 1;
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 PrPC-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 PrPC-null (Prnp0/0) 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 PrPC suggest that they may associate and function as a complex in neurosphere-derived stem cells. The formation of neurospheres from Prnp0/0 mice was reduced significantly when compared with their wild-type counterparts. In addition, blockade of secreted STI1, and its cell surface ligand, PrPC, with specific antibodies, impaired Prnp+/+ neurosphere formation without further impairing the formation of Prnp0/0 neurospheres. Alternatively, neurosphere formation was enhanced by recombinant STI1 application in cells expressing PrPC but not in cells from Prnp0/0 mice. The STI1-PrPC 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-PrPC 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