Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation

• Published in: Nature biotechnology Vol. 22; no. 6; pp. 707 - 716
• Main Authors: Brandenberger, Ralph, Wei, Henry, Zhang, Sally, Lei, Shirley, Murage, Jaji, Fisk, Gregory J, Li, Yan, Xu, Chunhui, Fang, Rixun, Guegler, Karl, Rao, Mahendra S, Mandalam, Ramumkar, Lebkowski, Jane, Stanton, Lawrence W
• Format: Journal Article
• Language: English
• Published: New York, NY Nature 01.06.2004; Nature Publishing Group
• Subjects: Antigens, CD - genetics; Antigens, CD - physiology; Biological and medical sciences; Biotechnology; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cell Differentiation - physiology; Cell Division - drug effects; Cell Division - genetics; Cell Division - physiology; Cell Line; Cytokine Receptor gp130; Dimethyl Sulfoxide - pharmacology; Diverse techniques; Down-Regulation - drug effects; Down-Regulation - genetics; Embryo, Mammalian - cytology; Expressed Sequence Tags; Fibroblast Growth Factors - genetics; Fibroblast Growth Factors - physiology; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Gene Expression Profiling; Gene Library; Growth Substances - pharmacology; Health. Pharmaceutical industry; Humans; Industrial applications and implications. Economical aspects; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - physiology; Interleukin-6; Leukemia Inhibitory Factor; Membrane Glycoproteins - genetics; Membrane Glycoproteins - physiology; Miscellaneous; Molecular and cellular biology; Nodal Protein; Proteins - genetics; Proteins - physiology; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - physiology; Receptors, Fibroblast Growth Factor - genetics; Receptors, Fibroblast Growth Factor - physiology; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA - genetics; RNA - isolation & purification; Sequence Analysis, DNA; Signal Transduction - genetics; Signal Transduction - physiology; Stem Cells - cytology; Stem Cells - metabolism; Transcription Factors - genetics; Transcription Factors - physiology; Transcription, Genetic - genetics; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - physiology; Tretinoin - pharmacology; Up-Regulation - drug effects; Up-Regulation - genetics; Wnt Proteins; Human; Cell proliferation; Embryo; Regulation(control); Stem cell; Transcriptome; Cell differentiation; Gene expression; Expressed sequence tag
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt971

Human embryonic stem (hES) cells hold promise for generating an unlimited supply of cells for replacement therapies. To characterize hES cells at the molecular level, we obtained 148,453 expressed sequence tags (ESTs) from undifferentiated hES cells and three differentiated derivative subpopulations. Over 32,000 different transcripts expressed in hES cells were identified, of which more than 16,000 do not match closely any gene in the UniGene public database. Queries to this EST database revealed 532 significantly upregulated and 140 significantly downregulated genes in undifferentiated hES cells. These data highlight changes in the transcriptional network that occur when hES cells differentiate. Among the differentially regulated genes are several components of signaling pathways and transcriptional regulators that likely play key roles in hES cell growth and differentiation. The genomic data presented here may facilitate the derivation of clinically useful cell types from hES cells.