A gene expression profile of embryonic stem cells and embryonic stem cell-derived neurons

Article type: Research Article

Authors: Loring, J.F. | Porter, J.G. | Seilhammer, J. | Kaser, M.R. | Wesselschmidt, R.

Affiliations: Department of Life Sciences, Incyte Genomics, Inc, 3160 Porter Drive, Palo Alto, CA 94304, USA

Note: [] Corresponding author: E-Mail: [email protected]

Abstract: Embryonic stem (ES) cells have the ability to differentiatie into a variety of cell lineages. We are examining ES cell differentiation in vitro by using cDNA microarrays to generate a molecular phenotype for each cell type. El4 ES cells induced by retinoic acid after forming embryoid bodies differentiatie almost exclusively to neurons. We obtained expression pattems for about 8500 gene sequenees by comparing mRNAs from undifferentiated ES cells and their differentiated derivatives in a competitive hybridization. Our results indicate that the genes expressed by ES cells change dramatically as they differentiatie (58 gene sequences up-regulated, 34 down-regulated). Most notably, totipotent ES cells expressed high levels of a repressor of Hox expression (the polycomb homolog Mphl) and a co-repressor (CTBP2). Expression of these genes was undetectable in differentiated cells; the ES cell-derived neurons expressed a different set of transcriptional regulators, as weil as markers of neurogenesis. The gene expression profiles indicate that ES cells actively suppress differentiation by transcriptional repression; cell-cell contact in embryoid bodies and retinoic acid treatment may overcome this suppression, allowing expression of Hox genes and inducing a suite of neuronal genes. Gene expression profiles will be a useful outcome measure for comparing in vitro treatrnents of differentiating ES cells and other stem cells. Also, knowing the molecule phenotype of transplantable cells will allow correlation of phenotype with the success of the transplant.

Keywords: Microarray, neural development, embryoid body, totipotence

Journal: Restorative Neurology and Neuroscience, vol. 18, no. 2-3, pp. 81-88, 2001