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


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.

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Figure 1: Identification of transcripts from human embryonic stem cells.
Figure 2: Expression of Leukemia Inhibitory Factor (LIF) gene family genes and their receptors in human ES cells based on EST frequencies (see Table 1b).
Figure 3: WNT pathway.
Figure 4: NODAL pathway summary.

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We thank Ellen Beasley, Melissa Carpenter, Dennis Gilbert, Joseph D. Gold, Calvin Harley, Greg Fisk, Gregg Morin and Catherine Priest for valuable discussions and Michael G. Walker for help with the statistical analysis. We acknowledge Jakyoung Agnew, Jerrod Denham, Kathaleen Golds, Robert Holt, Margaret Inokuma, Karen Ketchum, Michael Mok, Steven Rabkin and Tim Stockwell for expert technical assistance.

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Correspondence to Ralph Brandenberger.

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Several of the authors are or were employees of Geron Corporation or Celera Genomics.

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Brandenberger, R., Wei, H., Zhang, S. et al. Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nat Biotechnol 22, 707–716 (2004).

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