Coronavirus (COVID-19) updates for UC San Diego Health patients and visitors. Learn More

Menu
Search

Researchers Reveal Repressor Protein Blocks Neural Stem Cell Development

 

October 10, 2007  |  

A protein known to repress gene transcription at the molecular level in a variety of processes also blocks embryonic neural stem cells from differentiating into neurons, according to a study by University of California, San Diego and Howard Hughes Medical Institute (HHMI) researchers published online October 10 in Nature.

The research team focused on a repressor protein called SMRT (silencing mediator of retinoic acid and thyroid hormone receptor), which has been shown to repress gene expression in a number of molecular pathways.  By creating a strain of “knock-out” mice missing the SMRT gene, the team was able to pinpoint significant alterations in brain development in the absence of SMRT.  These findings demonstrate the important role of this protein in preventing premature differentiation of specific brain cells from undifferentiated neural stem cells in utero.

“By showing that SMRT prevents differentiation by maintaining neural stem cells in a basic stem cell state, we now have a target to study further how stem cells restrict themselves from differentiating,” said first author Kristen Jepsen, Ph.D., an assistant research scientist at the UC San Diego School of Medicine. 

The research team also noted that in the SMRT-deficient mice, the brain exhibited signs of excessive exposure to retinoic acid--naturally occurring vitamin A--which is a known teratogen (an agent which causes birth defects).  This finding suggests that in addition to maintaining neural stem cells in a pre-differentiated state, the SMRT protein controls retinoic-acid induced differentiation and, when missing, abnormalities that mimic vitamin A exposure occur.

This finding provides scientists with one more important key to understanding how stem cells maintain their potential to grow into specific cells. 

“Incremental steps such as this lay the groundwork for continuing studies investigating the potential of stem cells to be used therapeutically to replace damaged or deficient cells associated with disease,” said Jepsen.

Co-authors of the Nature paper are Derek Solum, PhD, Tianyuan Zhou, PhD, Robert McEvilly, PhD and Hyun-Jung Kim, PhD, of HHMI and UC San Diego; Christopher Glass, MD, PhD, professor of cellular and molecular medicine at UC San Diego; Ola Hermanson, PhD of the Karolinska Institute in Sweden, and senior author Michael G. Rosenfeld, M.D., HHMI investigator and professor of medicine at UC San Diego.

###

Media Contact: Leslie Franz, 619-543-6163, lfranz@ucsd.edu




Media Contact

Share This Article


Related News

9/21/2020
Moores Cancer Center at UC San Diego Health is using advanced imaging, genomics, personalized medicine and new therapies to treat patients like Brian McCloskey, who has stage IV prostate cancer.
9/17/2020
A consortium of 12 health systems, led by UC San Diego Health, introduces COVID19questions.org, a site where clinicians, researchers, patients and the general public are invited to submit questions th ...
9/16/2020
Early detection and intervention stanched the first known introductions of the SARS-CoV-2 virus into North America and Europe, validating the effectiveness of quick, comprehensive testing and contact ...
9/15/2020
UC San Diego Health is the first hospital on the West Coast to perform heart transplant surgery from a donor after circulatory death using a new portable organ care system. The investigational procedu ...



Follow Us