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 Study shines light on brain cells that coordinate movement
26.06.2017 | University of Washington Health Sciences/UW Medicine

nachricht New insight into a central biological dogma on ion transport
26.06.2017 | Aarhus University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Study shines light on brain cells that coordinate movement

26.06.2017 | Life Sciences

Smooth propagation of spin waves using gold

26.06.2017 | Physics and Astronomy

Switchable DNA mini-machines store information

26.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>