Abstract
Human embryonic stem (ES) cell lines that have the ability to self-renew and differentiate into specific cell types have been established. The molecular mechanisms for self-renewal and differentiation, however, are poorly understood. We determined the transcriptome profiles for two proprietary human ES cell lines (HES3 and HES4, ES Cell International), and compared them with murine ES cells and other human tissues. Human and mouse ES cells appear to share a number of expressed gene products although there are numerous notable differences, including an inactive leukemia inhibitory factor pathway and the high preponderance of several important genes like POU5F1 and SOX2 in human ES cells. We have established a list of genes comprised of known ES-specific genes and new candidates that can serve as markers for human ES cells and may also contribute to the "stemness" phenotype. Of particular interest was the downregulation of DNMT3B and LIN28 mRNAs during ES cell differentiation. The overlapping similarities and differences in gene expression profiles of human and mouse ES cells provide a foundation for a detailed and concerted dissection of the molecular and cellular mechanisms governing their pluripotency, directed differentiation into specific cell types, and extended ability for self-renewal.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caenorhabditis elegans Proteins / genetics
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Cell Differentiation / genetics*
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Cell Division / genetics
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Cell Line
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Cell Lineage / genetics*
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DNA (Cytosine-5-)-Methyltransferases / genetics
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DNA Methyltransferase 3A
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DNA Methyltransferase 3B
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DNA-Binding Proteins / genetics
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Down-Regulation / genetics
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Gene Expression Profiling
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Gene Expression Regulation, Developmental / genetics*
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Genetic Markers / genetics*
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Genome, Human
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Genotype
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HMGB Proteins
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Humans
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Interleukin-6 / genetics
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Leukemia Inhibitory Factor
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Mice
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Nuclear Proteins / genetics
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Octamer Transcription Factor-3
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Phenotype
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Pluripotent Stem Cells / cytology
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Pluripotent Stem Cells / metabolism*
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RNA, Messenger / analysis
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RNA, Messenger / metabolism
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Repressor Proteins / genetics
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SOXB1 Transcription Factors
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Transcription Factors / genetics
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Transcription, Genetic / genetics
Substances
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Caenorhabditis elegans Proteins
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DNA-Binding Proteins
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DNMT3A protein, human
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Genetic Markers
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HMGB Proteins
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Interleukin-6
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LIF protein, human
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LIN-28 protein, C elegans
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Leukemia Inhibitory Factor
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Lif protein, mouse
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Nuclear Proteins
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Octamer Transcription Factor-3
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POU5F1 protein, human
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Pou5f1 protein, mouse
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RNA, Messenger
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Repressor Proteins
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SOX2 protein, human
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SOXB1 Transcription Factors
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Sox2 protein, mouse
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Transcription Factors
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DNA (Cytosine-5-)-Methyltransferases
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DNA Methyltransferase 3A