Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Putting MicroRNAs on the Stem Cell Map

11.08.2008
Short snippets of RNA called microRNAs help to keep embryonic stem cells in their stem cell state. Researchers now have discovered the gene circuitry that controls microRNAs in embryonic stem cells. Mapping the control circuitry of stem cells reveals how they maintain themselves or decide to differentiate, providing key clues for regenerative medicine and reprogramming of adult cells to a stem cell state. These maps also aid our understanding of human development and diseases such as cancer.

Embryonic stem cells are always facing a choice—either 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.”

The work was supported by the National Institutes of Health.

Richard Young’s primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology at Massachusetts Institute of Technology.

Full citation:
Cell, August 8, 2008 134(5)
“Connecting microRNA Genes to the Core Transcriptional Regulatory Circuitry of Embryonic Stem Cells”

Alexander Marson (1,2,5), Stuart S. Levine (1,5), Megan F. Cole (1,2), Garrett M. Frampton (1,2), Tobias Brambrink (1), Sarah Johnstone (1,2), Matthew G. Guenther (1), Wendy K. Johnston (1,3), Marius Wernig (1), Jamie Newman (1, 2), J.Mauro Calabrese (2, 4), Lucas M. Dennis (1,2), Thomas L. Volkert (1), Sumeet Gupta (1), Jennifer Love (1), Nancy Hannett (1), Phillip A. Sharp (2,4), David P. Bartel (1, 2, 3), Rudolf Jaenisch (1,2), and Richard A. Young (1,2)

1 Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
2 Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, MA
02139, USA
3 Howard Hughes Medical Institute
4 Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA

5 These authors contributed equally to this work

Cristin Carr | Newswise Science News
Further information:
http://www.wi.mit.edu/

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>