Featured Research

from universities, journals, and other organizations

Wide variety of genetic splicing in embryonic stem cells identified

Date:
March 21, 2010
Source:
Stanford University Medical Center
Summary:
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. Now researchers have shown that this tuning process is accomplished in part by restricting the number of messages, called transcripts, produced from each gene.

Michael Snyder's research sheds light on the flexibility exhibited by embryonic stem cells.
Credit: Steve Fisch Photography

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.

"We've identified an extremely comprehensive suite of neural-specific transcripts that will be very powerful," said Snyder. "We can begin to study neural differentiation with a degree of precision that's never been dreamed of before."

Snyder is the Stanford W. Ascherman, MD, FACS, Professor in Genetics and a member of Stanford's Cancer Center. He is the senior author of the research, which will be published online March 1 in the Proceedings of the National Academy of Sciences. The study's first author is postdoctoral scholar Jia Qian Wu, PhD.

One way to understand gene splicing is to think of it like this: Genes are made up of several "words" of DNA called exons. These exons are separated from one another on the cell's raw genetic material by intervening bits of unexpressed DNA. By changing the way the exons are joined, or spliced, together in the final RNA transcript, the cell can generate several related, yet distinct, protein products, or "sentences" from each gene. These RNA variants are called RNA isoforms -- and they're important in many biological processes, from generating antibodies to detoxifying drugs.

Snyder and Wu used a method of RNA sequencing Snyder invented while at Yale University called RNA-Seq to track the many RNA isoforms found at varying levels in human embryonic stem cells. The technique can identify a much greater range of RNA transcript levels and is much more sensitive than more traditional methods like DNA microarray analysis. That means it's possible to more reliably detect rare isoforms, and, as a result, more accurately plumb the secret transcriptional life of an embryonic stem cell -- which turns out to be richer than previously imagined.

"The average human gene is known to have four or five transcripts," said Snyder. "But that number will likely go much higher now with this new technology. We are measuring these with a degree of specificity that's never been possible before." Choosing which genes to express, and then how to splice those genes, adds a layer of complexity that allows a cell to fine-tune its final protein profile.

The researchers chose to study neural differentiation in a laboratory dish, rather than in the brain, because it's possible to start with and follow populations of purified cells. They monitored the variety of RNA isoforms found in the human embryonic stem cells and compared them to those found in the cells as they were coaxed through three stages of differentiation into neural cells called glia. At each stage, they found, the variety of isoforms in the cells decreased -- a phenomenon they termed "isoform specialization" -- as they settled into their chosen station.

When the researchers looked more closely, they saw that the isoforms remaining were involved in key neural signaling pathways or cellular receptors. Furthermore, at the earliest stages of their differentiation, the nascent glial cells contain isoforms for receptors found on many other types of neural cells -- suggesting they could be induced down several other developmental pathways.

Finally, the value of the researcher's transcript "dictionary" is hinted at by the finding that the timing of expression of two genes important in neural differentiation -- SOX1 and PAX6 -- in humans is different than that observed in mice.

Snyder and Wu collaborated with researchers from Yale University, Imperial College London and 454 Life Sciences Sequencing Center in Branford, Conn., to conduct the research. The research was supported by the National Institutes of Health, the state of Connecticut and the IOG Trust.


Story Source:

The above story is based on materials provided by Stanford University Medical Center. The original article was written by Krista Conger. Note: Materials may be edited for content and length.


Journal Reference:

  1. Jia Qian Wu, Lukas Habegger, Parinya Noisa, Anna Szekely, Caihong Qiu, Stephen Hutchison, Debasish Raha, Michael Egholm, Haifan Lin, Sherman Weissman, Wei Cui, Mark Gerstein, and Michael Snyder. Dynamic transcriptomes during neural differentiation of human embryonic stem cells revealed by short, long, and paired-end sequencing. Proceedings of the National Academy of Sciences, 2010; 107 (11): 5254-5259 DOI: 10.1073/pnas.0914114107

Cite This Page:

Stanford University Medical Center. "Wide variety of genetic splicing in embryonic stem cells identified." ScienceDaily. ScienceDaily, 21 March 2010. <www.sciencedaily.com/releases/2010/03/100301151921.htm>.
Stanford University Medical Center. (2010, March 21). Wide variety of genetic splicing in embryonic stem cells identified. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2010/03/100301151921.htm
Stanford University Medical Center. "Wide variety of genetic splicing in embryonic stem cells identified." ScienceDaily. www.sciencedaily.com/releases/2010/03/100301151921.htm (accessed July 29, 2014).

Share This




More Health & Medicine News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins