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Regulating Embryonic Stem Cell Self-Renewal

10/15/2007

In the October 15th issue of G&D, Dr. Huck-Hui Ng and colleagues at the Genome Institute of Singapore identify two genes – called Jmjd1a and Jmjd2c – that regulate self-renewal in embryonic stem cells. This finding will have important ramifications for embryonic stem cell research.

"These are new pathways that the ES cell uses to counteract inappropriate silencing of key pluripotency genes. Perturbation of these pathways affects the maintenance of ES cells," explains Dr. Ng.

Embryonic stem cells (ES cells) are pluripotent: They can differentiate into any of the specialized cell types of the body (excluding the placenta), as well as new, undifferentiated (unspecialized) stem cells (a process known as "self-renewal"). Understanding the genetic basis of self-renewal is integral to the long-term maintenance of viable ES cell lines.

Dr. Ng and colleagues investigated how modifications to chromatin structure influence gene transcription and ES cell function. The researchers found that Jmjd1a and Jmjd2c, which encode enzymes that demethylate histone H3 lysine 9, regulate self-renewal in mouse ES cells: Depletion of Jmjd1a and Jmjd2c promoted differentiation, at the expense of self-renewal. Thus, these two histone modifying enzymes are required for maintaining pluripotency of ES cells.

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