DNA microarray analysis of differential gene expression of 6-year-old rat neural striatal progenitor cells during early differentiation

Article type: Research Article

Authors: Zhou, Feng C.^; | Duguid, John R.^; | Edenberg, Howard J.^; | McClintick, Jeanette | Young, Peter | Nelson, Paul

Affiliations: Departments of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA | Medical Neurobiology Program Indiana University School of Medicine, Indianapolis, IN 46202, USA | Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA | Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA | Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA | Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN 46202, USA | Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA

Note: [] Corresponding author: Dr. Feng C. Zhou, Indiana University School Medicine, Department of Anatomy and Ceil Biology, MS 508,635 Dr. Indianapolis, IN 46202, USA. Tel.: +1 317 274 7359; Fax: +1 317 2040; E-mail: [email protected].

Abstract: EGF-responsive striatal progenitor cells from rat brain have been maintained in culture in the form of neurospheres for six years without exhausting their renewal capacity. The events surrounding differentiation of stem cells in the brain after a long progenitorship remain a mystery. Using DNA microarray analysis we investigated differential gene expression, comparing progenitor cells in their neurosphere state with the cells 24 hours after induction of differentiation. Eighty-one genes showed increased expression in the differentiated condition. Genes associated with cellular growth, neurite outgrowth, and synaptogenesis were activated, including both anti-apoptotic and pro-apoptotic genes. Two transmitter- related genes, acetylcholine receptor-ß and glutamate receptor-ß-unit were also elevated-, these genes not only fit the profile of early neural development, but also reflect the characteristics of striatal neurons. In addition, there are approximately 30 expressed sequence tags (ES7) increased during neural differentiation. Forty-seven genes showed decreased expression; half of them are known genes related to the cell cycle, cell adhesion, transcription, and signaling. Tbe signaling and cell cycle genes may be responsible for the life-long self-renewal. These data demonstrate for the first time that life-long quiescent stem cells retain the potential to become activated and develop into specific types of brain cells. The six-year long-term neural stem cells are an excellent model for studying developmental neurobiological processes and aging.

Keywords: neural stem cells, genomics, microarray, gene expression, apoptosis, signal transduction, aging, development,

Journal: Restorative Neurology and Neuroscience, vol. 18, no. 2-3, pp. 95-104, 2001