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

Nature Biotechnology volume 22, pages 707–716 (2004)Cite this article

Abstract

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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Acknowledgements

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.

Author information

Author notes

  1. Sally Zhang

    Present address: Transplantation Immunology, Department of Cardiothoracic Surgery, Stanford University, Stanford, California, 94305, USA

  2. Shirley Lei

    Present address: UCSF School of Dentistry, 513 Parnassus Avenue, S-630, San Francisco, California, 94143-0430, USA

  3. Jaji Murage

    Present address: Molecular Pharmacology, Stanford University, 269 Campus Drive, CCSR 3230, Stanford, California, 94305, USA

  4. Rixun Fang & Karl Guegler

    Present address: Applied Biosystems, 850 Lincoln Centre Drive, Foster City, California, 94404, USA

  5. Lawrence W Stanton

    Present address: Genome Institute of Singapore, 60 Biopolis Street, Singapore, 138672

Authors and Affiliations

  1. Geron Corporation, 230 Constitution Drive, Menlo Park, California, 94025, USA

    Ralph Brandenberger, Henry Wei, Sally Zhang, Shirley Lei, Jaji Murage, Gregory J Fisk, Yan Li, Chunhui Xu, Ramumkar Mandalam, Jane Lebkowski & Lawrence W Stanton

  2. Celera Genomics, 45 West Gude Drive, Rockville, 20850, Maryland, USA

    Rixun Fang & Karl Guegler

  3. National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, 21224, Maryland, USA

    Mahendra S Rao

  4. Transplantation Immunology, Department of Cardiothoracic Surgery, Stanford University, Stanford, California, 94305, USA

    Shirley Lei, Jaji Murage, Rixun Fang, Karl Guegler & Lawrence W Stanton

  5. UCSF School of Dentistry, 513 Parnassus Avenue, S-630, San Francisco, California, 94143-0430, USA

    Sally Zhang, Jaji Murage, Rixun Fang, Karl Guegler & Lawrence W Stanton

  6. Molecular Pharmacology, Stanford University, 269 Campus Drive, CCSR 3230, Stanford, California, 94305, USA

    Sally Zhang, Shirley Lei, Rixun Fang, Karl Guegler & Lawrence W Stanton

  7. Applied Biosystems, 850 Lincoln Centre Drive, Foster City, California, 94404, USA

    Sally Zhang, Shirley Lei, Jaji Murage & Lawrence W Stanton

  8. Genome Institute of Singapore, 60 Biopolis Street, Singapore, 138672

    Sally Zhang, Shirley Lei, Jaji Murage, Rixun Fang & Karl Guegler

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Correspondence to Ralph Brandenberger.

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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). https://doi.org/10.1038/nbt971

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