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Catalog of gene expression in adult neural stem cells and their in vivo microenvironment
KTH, School of Biotechnology (BIO), Gene Technology.ORCID iD: 0000-0002-0602-2062
KTH, School of Biotechnology (BIO), Gene Technology.ORCID iD: 0000-0003-3811-5439
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2006 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 312, no 10, 1798-1812 p.Article in journal (Refereed) Published
Abstract [en]

 Stem cells generally reside in a stem cell micro environment, where cues for self-renewal and differentiation are present. However, the genetic program underlying stem cell proliferation and multipotency is poorly understood. Transcriptome analysis of stem cells and their in vivo microenvironment is one way of uncovering the unique sternness properties and provides a framework for the elucidation of stem cell function. Here, we characterize the gene expression profile of the in vivo neural stem cell microenvironment in the lateral ventricle wall of adult mouse brain and of in vitro proliferating neural stem cells. We have also analyzed an Lhx2-expressing hematopoietic-stem-cell-like cell line in order to define the transcriptome of a well-characterized and pure cell population with stem cell characteristics. We report the generation, assembly and annotation of 50,792 high-quality 5'-end expressed sequence tag sequences. We further describe a shared expression of 1065 transcripts by all three stem cell libraries and a large overlap with previously published gene expression signatures for neural stem/progenitor cells and other multipotent stem cells. The sequences and cDNA clones obtained within this framework provide a comprehensive resource for the analysis of genes in adult stem cells that can accelerate future stem cell research.

Place, publisher, year, edition, pages
2006. Vol. 312, no 10, 1798-1812 p.
Keyword [en]
Digital signature, EST, Gene expression, Lateral ventricle wall, Microenvironment, Neural stem cell, Neurosphere, Transcriptome
National Category
Biological Sciences
URN: urn:nbn:se:kth:diva-6166DOI: 10.1016/j.yexcr.2006.02.012ISI: 000238179100010ScopusID: 2-s2.0-33646714932OAI: diva2:10798
QC 20100902Available from: 2006-09-22 Created: 2006-09-22 Last updated: 2010-09-02Bibliographically approved
In thesis
1. Mining the transcriptome - methods and applications
Open this publication in new window or tab >>Mining the transcriptome - methods and applications
2006 (English)Doctoral thesis, comprehensive summary (Other scientific)
Abstract [en]

Regulation of gene expression occupies a central role in the control of the flow of genetic information from genes to proteins. Regulatory events on multiple levels ensure that the majority of the genes are expressed under controlled circumstances to yield temporally controlled, cell and tissue-specific expression patterns. The combined set of expressed RNA transcripts constitutes the transcriptome of a cell, and can be analysed on a large-scale using both sequencing and microarray-based methods.

The objective of this work has been to develop tools for analysis of the transcriptomes (methods), and to gain new insights into several aspects of the stem cell transcriptome (applications). During recent years expectations of stem cells as a resource for treatment of various disorders have emerged. The successful use of endogenously stimulated or ex vivo expanded stem cells in the clinic requires an understanding of mechanisms controlling their proliferation and self-renewal.

This thesis describes the development of tools that facilitate analysis of minute amounts of stem cells, including RNA amplification methods and generation of a cDNA array enriched for genes expressed in neural stem cells. The results demonstrate that the proposed amplification method faithfully preserves the transcript expression pattern. An analysis of the feasibility of a neurosphere assay (in vitro model system for study of neural stem cells) clearly shows that the culturing induces changes that need to be taken into account in design of future comparative studies. An expressed sequence tag analysis of neural stem cells and their in vivo microenvironment is also presented, providing an unbiased large-scale screening of the neural stem cell transcriptome. In addition, molecular mechanisms underlying the control of stem cell self-renewal are investigated. One study identifies the proto-oncogene Trp53 (p53) as a negative regulator of neural stem cell self-renewal, while a second study identifies genes involved in the maintenance of the hematopoietic stem cell phenotype.

To facilitate future analysis of neural stem cells, all microarray data generated is publicly available through the ArrayExpress microarray data repository, and the expressed sequence tag data is available through the GenBank.

Place, publisher, year, edition, pages
Stockholm: KTH, 2006. 62 p.
Theses in philosophy from the Royal Institute of Technology, ISSN 1650-8831
transcriptome, gene expression profiling, EST, microarray, RNA amplification, stem cells, neurosphere
National Category
Other Industrial Biotechnology
urn:nbn:se:kth:diva-4115 (URN)91-7178-436-5 (ISBN)
Public defence
2006-10-13, FR4, AlbaNova Universitetscentrum, Roslagstullsbacken 21, Stockholm, 10:00
QC 20100927Available from: 2006-09-22 Created: 2006-09-22 Last updated: 2010-09-27Bibliographically approved

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