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Researchers discover key to human embryonic stem-cell potential

s in maintaining stem cell identity--if they are disabled, the stem cell immediately begins to differentiate and is thus no longer a stem cell. "But we did not know how these proteins instructed stem cells to be pluripotent," says Laurie Boyer, first author on the paper and a postdoctoral scientist who divides her time between the Jaenisch and Young labs.

Using a microarray technology invented in the Young lab, Boyer and her colleagues analyzed the entire genome of a human embryonic stem cell and identified the genes regulated by these three transcription factors. The research team discovered that while these transcription factors activate certain genes essential for cell growth, they also repress a key set of genes needed for an embryo to develop.

This key set of repressed genes produce additional transcription factors that are responsible for activating entire networks of genes necessary for generating many different specialized cells and tissues. Thus, Oct4, Sox2, and Nanog are master regulators, silencing genes that are waiting to create the next generation of cells. When Oct4, Sox2, and Nanog are inactivated as the embryo begins to develop, these networks then come to life, and the stem cell ceases to be a stem cell.

The new work provides the first wiring diagram of human embryonic stem-cell regulatory circuitry. "This gives us a framework to further understand how human development is regulated," says Boyer.

"These findings provide the foundation for learning how to modify the circuitry of embryonic stem cells to repair damaged or diseased cells or to make cells for regenerative medicine," says Young. "They also establish the foundation for solving circuitry for all human cells."


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Source:Whitehead Institute for Biomedical Research


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