International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

I25. Mouse Embryonic Stem (ES) Cell Neural Differentiation: Identification of a Substantial Number of Novel, Uncharacterized, And Disease-Related Expressed Sequence Tags (ESTs)

M. A. Wride1, F. C. Mansergh1, G. Bain1, J. Hance1, Y. Yoshimura2, A Isogawa2, T. Tsuzuki2, D. E. Rancourt1, 1Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Drive N.W., Calgary, Alberta, Canada T2N 4N1 and
Department of Medical Biophysics and Radiation Biology, Graduate School of Medical Sciences, Kyushu University, 1-1, Maidashi 3-chome, Higashi-ku, Fukuoka, 812-8582, Japan.

We have developed methods for synchronously differentiating murine embryonic stem (ES) cells into functional neurons and glia in vitro. Using this system, we have used a subtractive hybridization approach to isolate to date 612 independent expressed sequence tags (ESTs) of which 96 (16%) have no significant matches when analyzed using BLAST. These ESTs have thus been deemed novel. A further 191 ESTs (31%) match uncharacterized sequences already in the database (ESTs or genomic sequences), but for which there is no known function. This system has thus provided 288 novel or uncharacterized ESTs. Expression studies of several novel ESTs have revealed that they are preferentially expressed in the embryonic central nervous system (CNS). Notably, of 325 known genes identified, 45 are associated with numerous diseases including cancers and a number of syndromes in which mental retardation is a feature. Full length sequence, expression and functional data for the novel genes identified, using both bench and bioinformatic approaches, will be relevant to basic and applied aspects of nervous system development and disease and to drug discovery. Furthermore, this system has provided valuable data with regard to patterns of gene expression during early neural differentiation and given recent advances in ES and neural stem cell cytotherapeutics, further characterization of this system is a priority. (Supported by the ACB, AHFMR, MRC of Canada, and NIH).

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