Navigation Links
Putting microRNAs on the stem cell map
Date:8/7/2008

CAMBRIDGE, Mass. (August 7, 2008) Embryonic stem cells are always facing a choiceeither to self-renew or begin morphing into another type of cell altogether.

It's a tricky choice, governed by complex gene regulatory circuitry driven by a handful of key regulators known as "master transcription factors," proteins that switch gene expression on or off.

In the past few years, scientists in the lab of Whitehead Member Richard Young and their colleagues have mapped out key parts of this regulatory circuitry, but the genes that produce the tiny snippets of RNA known as microRNAs have until now been a missing piece of the map. Since microRNAs are a second set of regulators that help to instruct stem cells whether to stay in that state, they play key roles in development.

Young and colleagues have now discovered how microRNAs fit into the map of embryonic stem cell circuitry. With this map, the scientists have moved one step closer to understanding how adult cells can be reprogrammed to an embryonic state and then to other types of cells, and to understanding the role of microRNAs in cancer and other diseases.

"By understanding how master transcription factors turn microRNAs on and off, we now see how these two groups of gene regulators work together to control the state of the cell," says Young, senior author on the study reported in the August 8 issue of Cell. "MicroRNAs are a special class of molecules because they not only contribute to cellular control but they play important roles in disease states such as cancer."

Previous studies had shown that the microRNA machinery is important in maintaining embryonic stem cells in their embryonic state, but offered only partial views of how microRNA genes fit in with the overall gene regulation circuitry. To do so required mapping the sites in the genome from which microRNA genes start, explains Stuart Levine, co-lead author on the paper and postdoctoral scientist in Young's lab.

"Knowing where genes start is essential to understanding their control," says Levine. "Based on our knowledge of microRNA gene start sites we were able to discover how these genes are controlled by the master transcription factors."

The researchers first created genome-wide maps of human and mouse embryonic stem cells that pinpoint where transcription factors bind to DNA and launch gene expression. This pinpointed where four master transcription factors (known as Oct4, Sox2, Nanog and Tcf3) were occupying sites where microRNA genes start to be transcribed. They found that the four core transcription factors are interacting with two key sets of microRNA genes. One set of microRNA genes is actively expressed in embryonic stem cells. The other set is silenced in those cells by other gene regulatory proteins known as Polycomb proteins. These proteins repress genes that are key for later development, a role previously described by Young lab researchers and their colleagues.

"We now have a list of what microRNAs are important in embryonic stem cells," says Alex Marson, co-lead author on the paper and an MD/PhD student in the Young lab. "This gives us clues of which microRNAs you might want to target to direct an embryonic stem cell into another type of cell. For example, you might be able to harness a microRNA to help drive an embryonic stem cell to become a neuron, aiding with neurodegenerative disease or spinal cord injury."

Moreover, the results give scientists a better platform for analyzing microRNA gene expression in cancer and other diseases. "We and others are finding that the overall gene circuitry for embryonic stem cells and cancer cells is very similar," notes Marson. "Now that we have connected the circuitry to microRNAs, we can begin to compare microRNAs that are regulated in embryonic stem cells to those in cancer cells."


'/>"/>

Contact: Cristin Carr
carr@wi.mit.edu
617-324-0460
Whitehead Institute for Biomedical Research
Source:Eurekalert

Related medicine news :

1. When it comes to putting, Tiger and Nicklaus might not have best advice
2. When it comes to putting, Tiger and Nicklaus
3. Putting Health Before Politics: How the United States Senate Can Fix Global HIV/AIDS Funding
4. Targeting aggressive breast cancers by putting them to sleep
5. VA Putting Mobile Pharmacies on the Road
6. U.S. Soccer Team Putting Vision in Focus for the Beijing 2008 Olympic Games
7. Putting an End to Medical Cruelty: A Horrifying Article in Yahoo this Week by T. L. Kittle
8. Putting the Medical Profession on Notice!: Widow Tells Tragic Story of How Her Husband Died Due to Misdiagnosis and Mistreatment
9. Putting on Pedometer Helps Walkers Shed Pounds
10. Putting risk in perspective: Do people make better decisions when they understand average risk?
11. AUDIO from Medialink and P&G: Putting Your Smile in Hollywoods Spotlight
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/12/2016)... ... ... Trends: , Back to the Future , Feb. 25, 2016 — 11:00 a.m. – 12:30 ... don’t learn from history are doomed to repeat it.” , An analysis of CDRH’s enforcement ... that takes time. , Take a close look at the warning letters the agency ...
(Date:2/12/2016)... ... February 12, 2016 , ... T.E.N., a technology ... for the ISE Southeast Awards 2016. Finalists and winners of the ISE® Awards ... Executive Forum and Awards Gala on March 15, 2016 at the Westin Peachtree ...
(Date:2/12/2016)... ... February 12, 2016 , ... AssureVest Insurance Group, a locally owned insurance ... drive that will raise funds earmarked to purchase computers and software for Mrs. Harrison’s ... “My school is in a low-income area and has more than 60 2nd and ...
(Date:2/12/2016)... CA (PRWEB) , ... February 12, 2016 , ... Donor ... in northern California and Nevada, announced a partnership with San Ramon Regional Medical Center. ... to the hospital’s facilities as a way to accommodate a more certain time frame ...
(Date:2/12/2016)... ... February 12, 2016 , ... Nearly every health website and ... These articles generally list between five and 15 foods that should be consumed ... one of these lists and believes that nutritious eye healthy foods are extremely ...
Breaking Medicine News(10 mins):
(Date:2/12/2016)... and SEOUL, South Korea ... Biosys­tems Menarini and Macrogen, Inc. today announced they ... and innovative procedures for precision medicine in cancer. ... Silicon Biosystems, DEPArray™ digital-sorting technology with Macrogen,s high-throughput ... tests certified under the Clinical Laboratory Improvement Amendments ...
(Date:2/12/2016)... -- Aralez Pharmaceuticals Inc. (Nasdaq: ARLZ ) (TSX: ARZ), a ... the Nasdaq Closing Bell at the Nasdaq MarketSite in ... 4:00 p.m. ET on Tuesday, February 16, 2016 to ... Adams , will perform the honorary bell ringing ceremony ... A live webcast will be available at: https://new.livestream.com/nasdaq/live ...
(Date:2/12/2016)... WILMINGTON, North Carolina , 12 februari ... Laboratories, Inc. (AAI/CML), een toonaangevende leverancier van ... farmaceutische en biotechnologische industrieën, kondigt vandaag een ... en mogelijkheden op haar locatie in ... in vraag heeft geleid tot meerdere recente ...
Breaking Medicine Technology: