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The gene expression profile of PDGF-treated neural stem cells corresponds to partially differentiated neurons and glia
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2006 (English)In: Growth Factors, ISSN 0897-7194, E-ISSN 1029-2292, Vol. 24, no 3, 184-196 p.Article in journal (Refereed) Published
Abstract [en]

We have previously shown that platelet-derived growth factor AA (PDGF-AA) stimulates the expansion of neuronal progenitors from neural stem cells, but is unable to replace fibroblast-growth factor 2 (FGF-2) as a stem cell mitogen. In the present study, we compared gene expression in neural stem cells that were grown in the presence of FGF-2 and in cells cultured with PDGF-AA or in the absence of growth factor, which induces differentiation. The genetic program elicited by PDGF-AA (156 significantly regulated genes) was not unique, but an intermediate between the ones of FGF-2-cultured stem cells and differentiated cells. These observations are compatible with the hypothesis that PDGF-AA induces a partial differentiation of neural stem cells, which retain the ability to proliferate, rather than acting solely as an instructing agent for neuronal differentiation. Finally, the transcriptional signature of stem cells grown with FGF-2 included a large number of genes over-expressed in gliomas and a core set of conserved genes periodically expressed during the eukaryote cell cycle.

Place, publisher, year, edition, pages
2006. Vol. 24, no 3, 184-196 p.
Keyword [en]
PDGF, FGF-2, neural stem cell, microarray, differentiation, neuron
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-22419DOI: 10.1080/08977190600696430ISI: 000241724500004PubMedID: 17079202OAI: oai:DiVA.org:uu-22419DiVA: diva2:50192
Available from: 2007-03-06 Created: 2007-03-06 Last updated: 2014-10-03Bibliographically approved
In thesis
1. Neural Stem and Progenitor Cells: Cellular Responses to Known and Novel Factors
Open this publication in new window or tab >>Neural Stem and Progenitor Cells: Cellular Responses to Known and Novel Factors
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Neural stem cell self-renewal and differentiation are tightly regulated events during CNS development, leading to cell division into new neural stem cells or the formation of neurons and glial cells. This thesis focuses on the cellular responses induced by known and novel factors in neural stem and progenitor cells (NSPCs).

Platelet-derived growth factor (PDGF) signaling has previously been implicated in NSPC regulation as well as in tumor formation. In order to evaluate the differentiation process and find new regulators of NSPCs a micro-array screen was performed, evaluating transcription during normal differentiation and the effect of PDGF-AA in this process. The transcriptional profile of PDGF-AA treated NSPCs was shown to be an intermediate between the profiles of neural stem cells and their progeny. The NSPC transcriptome was also found to have similarities with that of experimental glioma. A previously non-characterized transcript, the nuclear receptor binding protein 2 (NRBP2), was identified and found to be expressed in the developing and adult mouse brain and in medulloblastoma. NRBP2 down-regulation rendered neural progenitors sensitive to induced cell death.

Different PDGF ligands interact with different combinations of PDGF receptors. Therefore NSPCs were stimulated with either PDGF-AA or -BB to further evaluate cellular responses with regard to the two specific isoforms. A divergent effect between the two isoforms in long-term proliferation and cell survival was found, with PDGF-BB being the most efficient stimulator.

Stem cell factor (SCF) has previously been identified as a regulator in the hematopoietic system and we showed that SCF induces a migratory response in NSPCs. In addition, SCF positively affected cell survival but had no effect on NSPC differentiation. Insights into the regulatory mechanisms involved in neural stem cell signaling are needed to develop diagnostic tools and novel treatments.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 63 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 504
neural stem cell, differentiation, proliferation, migration, PDGF, SCF, NRBP2, medulloblastoma
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Medical Biochemistry
urn:nbn:se:uu:diva-110722 (URN)978-91-554-7671-7 (ISBN)
Public defence
2010-01-15, B21, (BMC) Biomedical Center, Husargatan 3, Uppsala, 09:15 (English)
Available from: 2009-12-21 Created: 2009-11-23 Last updated: 2014-10-23Bibliographically approved

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Larsson, JimmyHeldin, Carl-HenrikForsberg-Nilsson, Karin
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Ludwig Institute for Cancer ResearchDepartment of Medical Biochemistry and Microbiology
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