Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Researchers Chart Epigenomics of Stem Cells That Mimic Early Human Development

Published: Friday, May 10, 2013
Last Updated: Friday, May 10, 2013
Bookmark and Share
Collaborative study will help overcome hurdles to using stem cells to treat diseases and injuries.

Scientists have long known that control mechanisms known collectively as "epigenetics" play a critical role in human development, but they did not know precisely how alterations in this extra layer of biochemical instructions in DNA contribute to development.

Now, in the first comprehensive analysis of epigenetic changes that occur during development, a multi-institutional group of scientists, including several from the Salk Institute for Biological Studies, has discovered how modifications in key epigenetic markers influence human embryonic stem cells as they differentiate into specialized cells in the body. The findings were published May 9, 2013 in Cell.

"Our findings help us to understand processes that occur during early human development and the differentiation of a stem cell into specialized cells, which ultimately form tissues in the body," says co-lead author Joseph R. Ecker, a professor and director of Salk's Plant Molecular and Cellular Biology Laboratory and holder of the Salk International Council Chair in Genetics.

Scientists have established that the gene expression program encoded in DNA is carried out by proteins that bind to regulatory genes and modulate gene expression in response to environmental cues. Growing evidence now shows that maintenance of this process depends on epigenetic marks such as DNA methylation and chromatin modifications, biochemical processes that alter gene expression as cells divide and differentiate from embryonic stem cells into specific tissues. Epigenetic modifications—collectively known as the epigenome—control which genes are turned on or off without changing the letters of the DNA alphabet (A-T-C-G), providing cells with an additional tool to fine-tune how genes control the cellular machinery.

In their study, the Salk researchers and their collaborators from several prominent research institutions across the United States examined the beginning state of cells, before and after they developed into specific cell types. Starting with a single cell type—the H1 human embryonic stem cell, the most widely studied stem cell line to date—the team followed the cells' epigenome from development to different cell states, looking at the dynamics in changes to epigenetic marks from one state to another. Were they methylated, an essential process for normal development, or unmethylated? What happened to the cells during development? What regulatory processes occurred in the cell lineage?

The scientists found sections of the DNA that activate regulatory genes, which in turn control the activity of other genes, tend to have different amounts of letters of the DNA alphabet, "C" and "G" specifically, depending on when these regulatory genes are turned on during development. Additionally, regulatory genes that control early development are often located on stretches of DNA called methylation valleys, or DMVs, that are generally CG rich and devoid of epigenetic chemical modifications known as methylation. Consequently, these genes have to be regulated by another epigenetic mechanism, which the authors found were chemical changes called chromatin modifications. Chromatin is the mass of material—DNA and proteins—in a cell's nucleus that helps to control gene expression.

On the other hand, genes active in more mature cells whose tissue type is already determined tend to be CG poor and regulated by DNA methylation. The results suggest that distinct epigenetic mechanisms regulate early and late states of embryonic stem cell differentiation.

"Epigenomic studies of how stem cells differentiate into distinct cell types are a great way to understand early development of animals," says Ecker, who is also a Howard Hughes Medical Institute and Gordon and Betty Moore Foundation Investigator. "If we understand how these cells' lineages originate, we can understand if something goes right or wrong during differentiation. It's a very basic study, but there are implications for being able to produce good quality cell types for various therapies."

For example, says Matthew Schultz, a graduate student in Ecker's lab, "understanding how development plays out normally could give us clues about how to reverse the process and turn normal adult cells into stem cells to regenerate tissues."

One area where the findings may help is in the study of tumor development. In normal tissue, DMVs are unmethylated, but in cancer, especially breast, colon and lung cancer, they are hypermethylated, suggesting, says Ecker, that alterations in the DNA methylation machinery might be an important mechanism aiding tumor development. He says further investigation is required to develop a greater understanding of this process.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Epigenetic Variations Between Tissues
A Salk Institute-led team has generated a map of the human methylome, gaining insight into patterns of DNA methylation of various tissues.
Wednesday, June 03, 2015
Vital Step in Stem Cell Growth Revealed
Salk scientists' finding could aid regenerative and cancer therapies.
Thursday, May 07, 2015
Gene-Editing Technique Offers Hope For Hereditary Diseases
Salk scientists use molecular "scissors" to eliminate mitochondrial mutations in eggs and embryos.
Monday, April 27, 2015
Cellular Scissors Chop up HIV Virus
Salk scientists re-engineered the bacterial defense system CRISPR to recognize HIV inside human cells and destroy the virus, offering a potential new therapy.
Thursday, March 12, 2015
No Extra Mutations in Modified Stem Cells, Study Finds
New results ease previous concerns that gene-editing techniques-used to develop therapies for genetic diseases-could add unwanted mutations to stem cells.
Saturday, July 12, 2014
Salk Institute Receives $3M Gift for Ageing Research
The gift from the Glenn Foundation for Medical Research will allow the Institute to continue conducting research to understand the biology of normal human aging and age-related diseases.
Friday, May 23, 2014
Circadian Clock Gene Linked to Eating Schedule
Research from the Salk Institute has shown that mutations in the circadian genes could drive night eating syndrome.
Friday, May 23, 2014
Salk Institute and Stanford Lead New $40M Stem Cell Genomics Center
Collaborative research center will bridge genomics and stem cell projects to find new therapies.
Sunday, February 02, 2014
Salk Institute Awarded Historic $42 Million Grant to Establish Center for Genomic Medicine
World-renowned research facility receives largest single donation in its 53-year history.
Thursday, January 24, 2013
Chromosome "Anchors" Organize DNA during Cell Division
Salk discovery of new role for telomeres in cellular growth may shed light on aging and age-related diseases.
Wednesday, January 09, 2013
Salk Scientists Pinpoint Key Player in Parkinson's Disease Neuron Loss
Stem cell study may help to unravel how a genetic mutation leads to Parkinson's symptoms.
Tuesday, October 23, 2012
Cold Viruses Point the way to New Cancer Therapies
Cold viruses generally get a bad rap, but new findings by a team of scientists at the Salk Institute for Biological Studies suggest that these viruses might also be a valuable ally in the fight against cancer.
Thursday, October 18, 2012
Reprogramming Signature may help Overcome Barriers to Regenerative Medicine
Salk scientists show nine genes at heart of epigenetic changes in induced pluripotent stem cells.
Friday, September 21, 2012
Salk Stem-Cell Research Shows Promise in Sickle-Cell Disease
Salk Stem-Cell Research Shows Promise in Sickle-Cell Disease Researchers are using cells from sickle-cell patients to potentially cure the anemia-inducing condition that affects one in every 12 black Americans. The method developed by Salk researchers also may be used to reverse other disorders linked to the same gene mutation implicated in sickle-cell disease.
Friday, December 09, 2011
Editing Scrambled Genes in Human Stem Cells may Help Realize the Promise of Combined Stem Cell-gene Therapy
Researchers at the Salk Institute successfully edited a diseased gene in patient-specific induced pluripotent stem cells as well as adult stem cells.
Tuesday, May 24, 2011
Scientific News
New Tech Vastly Improves CRISPR/Cas9 Accuracy
A new CRISPR/Cas9 technology developed by scientists at UMass Medical School is precise enough to surgically edit DNA at nearly any genomic location, while avoiding potentially harmful off-target changes typically seen in standard CRISPR gene editing techniques.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Biologists Induce Flatworms to Grow Heads and Brains of Other Species
Findings shed light on role of a new kind of epigenetic signaling in evolution, could yield clues for understanding birth defects and regeneration.
Turning up the Tap on Microbes Leads to Better Protein Patenting
Mining millions of proteins could become faster and easier with a new technique that may also transform the enzyme-catalyst industry, according to University of California, Davis, researchers.
Mathematical Model Forecasts the Path of Breast Cancer
Chances of survival depend on which organs breast cancer tumors colonize first.
Exploring the Causes of Cancer
Queen's research to understand the regulation of a cell surface protein involved in cancer.
Ancient Viral Molecules Essential for Human Development
Genetic material from ancient viral infections is critical to human development, according to researchers at the Stanford University School of Medicine.
Tardigrade's Are DNA Master Thieves
Tardigrades, nearly microscopic animals that can survive the harshest of environments, including outer space, hold the record for the animal that has the most foreign DNA.
The Secret Behind the Power of Bacterial Sex
Migration between different communities of bacteria is the key to the type of gene transfer that can lead to the spread of traits such as antibiotic resistance, according to researchers at Oxford University.
Farming’s in Their DNA
Ancient genomes reveal natural selection in action.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos