Abstract
Embryonic stem (ES) cells are pluripotent stem cells derived from preimplantation stage embryos. ES cells proliferate infinitely while maintaining pluripotency. These properties make them attractive sources for stem cell therapies and regenerative medicine. However, undifferentiated ES cells produce tumors when transplanted, which may preclude their therapeutic usage. It is largely unknown why ES cells can possess tumorigenicity without having chromosomal abnormalities. In this chapter, we introduce the methods to identify genes that play roles in tumor-like properties of ES cells.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Evans M. J. and Kaufman M. H. (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154–156.
Martin G. R. (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma. Proc. Natl. Acad. Sci. USA 78, 7634–7638.
Freed C. R. (2002) Will embryonic stem cells be a useful source of dopamine neurons for transplant into patients with Parkinson’s disease? Proc. Natl. Acad. Sci. USA 99, 1755–1757.
Nichols J., Zevnik B., Anastassiadis K., et al. (1998) Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 95, 379–391.
Niwa H., Miyazaki J., and Smith A. G. (2000) Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat. Genet. 24, 372–376.
Chambers I., Colby D., Robertson M., et al. (2003) Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113, 643–655.
Mitsui K., Tokuzawa Y., Itoh H., et al. (2003) The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113, 631–642.
Smith A. G., Heath J. K., Donaldson D. D., et al. (1988) Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature 336, 688–690.
Williams R. L., Hilton D. J., Pease S., et al. (1988) Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature 336, 684–687.
Ying Q. L., Nichols J., Chambers I., and Smith A. (2003) BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell 115, 281–292.
Sato N., Meijer L., Skaltsounis L., Greengard P., and Brivanlou A. H. (2004) Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat. Med. 10, 55–63.
Di Cristofano A., Pesce B., Cordon-Cardo C., and Pandolfi P. P. (1998) Pten is essential for embryonic development and tumour suppression. Nat. Genet. 19, 348–355.
Sun H., Lesche R., Li D. M., et al. (1999) PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway. Proc. Natl. Acad. Sci. USA 96, 6199–6204.
Stiles B., Gilman V., Khanzenzon N., et al. (2002) Essential role of AKT-1/protein kinase B alpha in PTEN-controlled tumorigenesis. Mol. Cell Biol. 22, 3842–3851.
Takahashi K., Mitsui K., and Yamanaka S. (2003) Role of ERas in promoting tumour-like properties in mouse embryonic stem cells. Nature 423, 541–545.
Jirmanova L., Afanassieff M., Gobert-Gosse S., Markossian S., and Savatier P. (2002) Differential contributions of ERK and PI3-kinase to the regulation of cyclin D1 expression and to the control of the G1/S transition in mouse embryonic stem cells. Oncogene 21, 5515–5528.
Tokuzawa Y., Kaiho E., Maruyama M., et al. (2003) Fbx15 is a novel target of Oct3/4 but is dispensable for embryonic stem cell self-renewal and mouse development. Mol. Cell Biol. 23, 2699–2708.
Gassmann M., Donoho G., and Berg P. (1995) Maintenance of an extrachromosomal plasmid vector in mouse embryonic stem cells. Proc. Natl. Acad. Sci. USA 92, 1292–1296.
Morita S., Kojima T., and Kitamura T. (2000) Plat-E: an efficient and stable system for transient packaging of retroviruses. Gene Ther. 7, 1063–1066.
Niwa H., Masui S., Chambers I., Smith A. G., and Miyazaki J. (2002) Phenotypic complementation establishes requirements for specific POU domain and generic transactivation function of Oct3/4 in embryonic stem cells. Mol. Cell Biol. 22, 1526–1536.
Savatier P., Lapillonne H., van Grunsven L. A., Rudkin B. B., and Samarut J. (1996) Withdrawal of differentiation inhibitory activity/leukemia inhibitory factor up-regulates D-type cyclins and cyclin-dependent kinase inhibitors in mouse embryonic stem cells. Oncogene 12, 309–322.
Mountford P., Zevnik B., Duwel A., et al. (1994) Dicistronic targeting constructs: reporters and modifiers of mammalian gene expression. Proc. Natl. Acad. Sci. USA 91, 4303–4307.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Humana Press Inc.
About this protocol
Cite this protocol
Takahashi, K., Ichisaka, T., Yamanaka, S. (2006). Identification of Genes Involved in Tumor-Like Properties of Embryonic Stem Cells. In: Turksen, K. (eds) Embryonic Stem Cell Protocols. Methods in Molecular Biology, vol 329. Humana Press. https://doi.org/10.1385/1-59745-037-5:449
Download citation
DOI: https://doi.org/10.1385/1-59745-037-5:449
Publisher Name: Humana Press
Print ISBN: 978-1-58829-498-2
Online ISBN: 978-1-59745-037-9
eBook Packages: Springer Protocols