Wide Variety of Genetic Splicing in Embryonic Stem Cells Identified

Like tuning in to an elusive radio frequency in a busy city, human embryonic stem cells must sort through a seemingly endless number of options to settle on the specific genetic message, or station, that instructs them to become more-specialized cells in the body (Easy Listening, maybe, for skin cells, and Techno for neurons?). Now researchers at the Stanford University School of Medicine have shown that this tuning process is accomplished in part by restricting the number of messages, called transcripts, produced from each gene.


Most genes can yield a variety of transcripts through a process called splicing. Variations in the ways a gene is spliced can change the form and function of the final protein product. Nearly all our genes can be spliced in more than one way. This research is the first time, however, that splicing variety has been linked to the unprecedented developmental flexibility, or pluripotency, exhibited by embryonic stem cells.

"The embryonic stem cells are loaded with many splicing variants for each gene," said Michael Snyder, PhD, chair of Stanford's genetics department. "But as the cells differentiate and become more specialized, the number of types of transcripts decreases."

Snyder and his colleagues studied the changes in RNA transcript levels occurring as the embryonic stem cells were induced in a laboratory dish to differentiate into neural cells. (The creation of RNA transcripts is an intermediate step in the generation of proteins from DNA.) In the process they generated a unique "dictionary" of neural-specific splicing variants, or isoforms.