Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Putting MicroRNAs on the Stem Cell Map

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:

More articles from Life Sciences:

nachricht Signaling Pathways to the Nucleus
19.03.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht In monogamous species, a compatible partner is more important than an ornamented one
19.03.2018 | Max-Planck-Institut für Ornithologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

A new kind of quantum bits in two dimensions

19.03.2018 | Physics and Astronomy

Scientists have a new way to gauge the growth of nanowires

19.03.2018 | Materials Sciences

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Science & Research
Overview of more VideoLinks >>>