Featured Research

from universities, journals, and other organizations

Researchers Map Cells' Inner Landscapes

Date:
July 15, 2008
Source:
Broad Institute of MIT and Harvard
Summary:
Much of the field of stem cell biology and development remains uncharted territory. Just as famous explorers and astronomers mapped out landmasses and constellations, researchers are working fervently to chart the molecular landscapes within stem cells -- especially embryonic stem cells.

Researchers have used the latest genomic tools to map out the epigenetic landscape, which is shaped by DNA methylation and modifications to histone proteins. They have also examined the role that these marks may play in cellular reprogramming.
Credit: Image by Bang Wong, Broad Communications

Much of the field of stem cell biology and development remains uncharted territory. Just as famous explorers and astronomers mapped out landmasses and constellations, researchers are working fervently to chart the molecular landscapes within stem cells — especially embryonic stem cells.

Related Articles


A clearer understanding of the cells’ unique properties, particularly their ability to give rise to nearly any type of cell, could unlock fundamental questions about biology and may even spur novel ways to treat disease.

A team of researchers at the Broad Institute has helped break new ground in stem cell research through work described in two recent Nature papers. The most recently published study, appearing in the July 6 advance online issue, involves an effort to map regions of cells’ genomes marked by DNA methylation — one of several so-called ‘epigenetic’ modifications. If DNA is the blueprint of a living organism, epigenetic marks, often in the form of chemical tags called methyl groups, are the gatekeepers to that blueprint. When affixed to DNA or to its protein scaffold (called “chromatin”), methyl groups can enable genes to be switched on or off, orchestrating signals that allow cells in the body, which share the same DNA, to assume different forms and functions.

In work published last year, Broad Institute researchers applied genomic tools to map the methylation of chromatin proteins called histones across the genomes of several types of cells, including embryonic stem cells. To complete that “epigenomic” picture, they decided to expand their work to include DNA methylation. “We used some of the latest genomic technologies,” said co-first author Alex Meissner, “to address a question many have wondered about: what’s the role of DNA methylation in cell development and differentiation?”

A long road towards DNA methylation maps

Researchers from the Whitehead Institute, Harvard University and Harvard Medical School came together at the Broad Institute to analyze DNA methylation throughout the genomes of embryonic stem cells, as well as more developmentally mature cells.

Meissner, formerly a postdoctoral fellow in the Jaenisch laboratory at the Whitehead Institute and now a Harvard University assistant professor and Broad associate member, said the new DNA methylation maps are the result of a long-term effort to address fundamental questions about how epigenetic factors influence cell development.

Researchers are able to create these maps using a technique known as bisulphite DNA sequencing. Although epigenetic information generally cannot be read from the As, Gs, Cs, and Ts that make up the DNA code, it turns out that a special chemical, sodium bisulphite, actually makes it possible to detect epigenetic modifications. Just as fine powders help detectives identify otherwise invisible fingerprints, sodium bisulphite helps scientists visualize the spots in a cell’s genome that harbor methyl groups and the spots that do not. The technique offers detailed views of DNA methylation and can now be implemented on a large-scale due to advances in high-throughput sequencing technologies.

With these advanced technologies, the scientists created DNA methylation maps of embryonic stem cells, as well as cell types derived from them, signifying the first such maps of mammalian cells. Several findings stood out from careful analyses of the maps, the most notable of which was the correlation between DNA methylation and histone methylation. Just as a topographic map of steep terrain and a political map of countries and borders may show similar patterns, chromatin and methylation maps can be used individually, or, more effectively, together to see a clearer picture of the molecular landscape. “In the past, these two types of epigenetic marks were rarely studied together,” said Tarjei Mikkelsen, a graduate student at the Broad Institute and co-first author of the July 6 Nature paper. “By examining them as a whole, we now have one of the first integrated pictures of epigenetic changes during cellular development.”

By perusing the maps, the researchers, led by Broad director Eric Lander, were also able to pick out specific sites within the genome where methylation fluctuates as cells develop, such as when embryonic stem cells mature into neural cells. Peering more closely at these dynamic changes, they identified certain sites associated with developmental genes that become overly methylated.

“Hypermethylation can be a sign that nearby genes are inaccessible, permanently shut off. And it is something that’s commonly observed in the genomes of tumor cells,” said Meissner. “These maps as well as the approaches used to create them may help shed light on the role of DNA methylation in human cancers.”

Increasing the efficiency of reprogramming

DNA methylation was also at the core of the scientists’ earlier paper, published in July 3 print issue of Nature. That paper described several molecular hurdles that impede a powerful technique in stem cell research — a recently described laboratory procedure that can nudge adult cells into a more primitive, stem-cell like state. This cellular “reprogramming” is now the focus of intense interest as a potential way to artificially derive embryonic stem cells from readily available adult tissues, such as skin. The method, though, can be slow and inefficient, with most cells failing to be reprogrammed.

Epigenetic marks such as DNA methylation are thought to act like a kind of memory storage for cells, helping cells “remember” their identities by keeping certain genes turned off and others on. If that’s true, then reprogramming likely requires those memories to be reset or wiped clean, allowing cells to assume new identities. During the course of their research, the scientists discovered that some epigenetic information, particularly DNA methylation, is especially difficult to expunge, hindering the reprogramming process. They then showed that treating incompletely reprogrammed cells with a drug that temporarily inhibits DNA methylation could greatly increase the efficiency of the process.

“The same genes that are slow to respond to reprogramming are the genes we see hypermethylated early on in development,” Mikkelsen said  “Improving the low efficiency of the reprogramming process required circumventing this mechanism without disabling it permanently.”

Having a map of these mechanisms could help researchers orient themselves in genomic space and develop additional methods to steer cells safely through the entire reprogramming process. Perhaps, like explorers before them, researchers today will also come across new discoveries along the way that will fill in more of the epigenetic maps.

Other Broad researchers who contributed to these papers include Eric Lander, Andreas Gnirke, Xiaolan Zhang, Bradley Bernstein, Andrey Sivachenko, Hongcang Gu, Chad Nusbaum, and David Jaffe. Researchers from the Whitehead Institute, Massachusetts General Hospital, and Harvard Medical School also contributed to the research.


Story Source:

The above story is based on materials provided by Broad Institute of MIT and Harvard. The original article was written by Haley Bridger and Nicole Davis. Note: Materials may be edited for content and length.


Journal References:

  1. Meissner et al. Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature, 2008; DOI: 10.1038/nature07107
  2. Mikkelsen et al. Dissecting direct reprogramming through integrative genomic analysis. Nature, 2008; 454 (7200): 49 DOI: 10.1038/nature07056

Cite This Page:

Broad Institute of MIT and Harvard. "Researchers Map Cells' Inner Landscapes." ScienceDaily. ScienceDaily, 15 July 2008. <www.sciencedaily.com/releases/2008/07/080710124535.htm>.
Broad Institute of MIT and Harvard. (2008, July 15). Researchers Map Cells' Inner Landscapes. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2008/07/080710124535.htm
Broad Institute of MIT and Harvard. "Researchers Map Cells' Inner Landscapes." ScienceDaily. www.sciencedaily.com/releases/2008/07/080710124535.htm (accessed October 25, 2014).

Share This



More Plants & Animals News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deep Sea 'mushroom' Could Be Early Branch on Tree of Life

Deep Sea 'mushroom' Could Be Early Branch on Tree of Life

Reuters - Innovations Video Online (Oct. 24, 2014) — Miniature deep sea animals discovered off the Australian coast almost three decades ago are puzzling scientists, who say the organisms have proved impossible to categorise. Academics at the Natural History of Denmark have appealed to the world scientific community for help, saying that further information on Dendrogramma enigmatica and Dendrogramma discoides could answer key evolutionary questions. Jim Drury has more. Video provided by Reuters
Powered by NewsLook.com
Black Bear Cub Goes Sunday Shopping

Black Bear Cub Goes Sunday Shopping

Reuters - Light News Video Online (Oct. 23, 2014) — Price check on honey? Bear cub startles Oregon drugstore shoppers. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Dances With Wolves in China's Wild West

Dances With Wolves in China's Wild West

AFP (Oct. 23, 2014) — One man is on a mission to boost the population of wolves in China's violence-wracked far west. The animal - symbol of the Uighur minority there - is under threat with a massive human resettlement program in the region. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
Breakfast Debate: To Eat Or Not To Eat?

Breakfast Debate: To Eat Or Not To Eat?

Newsy (Oct. 23, 2014) — Conflicting studies published in the same week re-ignited the debate over whether we should be eating breakfast. Video provided by Newsy
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:

Strange & Offbeat Stories

 

Plants & Animals

Earth & Climate

Fossils & Ruins

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