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Regulation of neural stem cells by exogenous and endogenous PDGF.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Manuscript (Other academic)
Identifiers
URN: urn:nbn:se:uu:diva-90759OAI: oai:DiVA.org:uu-90759DiVA: diva2:163222
Available from: 2003-09-11 Created: 2003-09-11 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Neural Stem Cell Differentiation and Migration
Open this publication in new window or tab >>Neural Stem Cell Differentiation and Migration
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Neural stem cells are the precursors of neurons, astrocytes and oligodendrocytes. During neural development, the division of stem cells takes place close to the lumen of the neural tube, after which they migrate to their final positions within the central nervous system (CNS). Soluble factors, including growth factors, regulate neural stem cell proliferation, survival, migration and differentiation towards specific cell lineages.

This thesis describes the function of platelet-derived growth factor (PDGF) and stem cell factor (SCF) in neural stem cell regulation. PDGF was previously suggested to stimulate neuronal differentiation, but the mechanisms were not defined. This study shows that PDGF is a mitogen and a survival factor that expands a pool of immature cells from neural stem cells. The PDGF-treated cells can be stained by neuronal markers, but need further stimuli to continue their maturation. They can become either neurons or glia depending on the secondary instructive cues. Moreover, neural stem cells produce PDGF. Inhibition of this endogenous PDGF negatively affects the cell number in stem cell cultures. We find that SCF stimulates migration and supports the survival of neural stem cells, but that it has no effect on their proliferation or differentiation into neurons and glia. Intracellular signaling downstream from the receptors for PDGF and SCF includes activation of extracellular signal-regulated kinase (ERK). This investigation shows that active ERK is not needed for the differentiation of stem cells into neurons, at least not during early stages.

Neural stem cells have a future potential in the treatment of CNS disorders. To be able to use neural stem cells clinically we need to understand how their proliferation, differentiation, survival and migration are controlled. The results presented in this thesis increase our knowledge of how neural stem cells are regulated by growth factors.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 73 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1281
Keyword
Medicine, CNS, stem cells, neuron, PDGF, SCF, differentiation, migration, ERK, Medicin
National Category
Dermatology and Venereal Diseases
Research subject
Medical Biochemistry
Identifiers
urn:nbn:se:uu:diva-3546 (URN)91-554-5714-2 (ISBN)
Public defence
2003-10-03, B21, BMC, Uppsala, 13:15
Opponent
Supervisors
Available from: 2003-09-11 Created: 2003-09-11 Last updated: 2016-04-29Bibliographically approved

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