TorontoScientists have found a control switch that regulates stem cell "pluripotency," the capacity of stem cells to develop into any type of cell in the human body. The discovery reveals that pluripotency is regulated by a single event in a process called alternative splicing.
Alternative splicing allows one gene to generate many different genetic messages and protein products. The researchers found that in genetic messages of a gene called FOXP1, the switch was active in embryonic stem cells but silent in "adult" cellsthose that had become the specialized cells that comprise organs and perform functions.
"It opens the field to the fact that alternative splicing plays a really important role in stem cell pluripotency," said Prof. Benjamin Blencowe, principal investigator on the study and a Professor in the University of Toronto's Departments of Molecular Genetics and Banting and Best Department of Medical Research. "We're beginning to see an entirely new landscape of regulation, which will be crucial to our understanding of how to produce more effective pluripotent stem cells for therapeutic and research applications."
The findings were published in the current online edition of the scientific journal Cell.
Alternative splicing works by allowing different segments of genetic messages, also known as messenger RNAs, to be spliced in different combinations as the messages are copied from a gene's DNA. Those combinations make different messenger RNAs, which in turn become different proteins.
In stem cells, scientists have shown that a core set of proteins called transcription factors control pluripotency.
The splicing event discovered by Blencowe's team, including first author on the study Dr. Mathieu Gabut, changes the DNA binding properties of FOXP1 in a way that then controls the expression of the core pluripotency transcription factors, to facilitate maintenance of pluripotency. "As a mechanism that
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University of Toronto