Navigation Links
Human embryonic stem cells remain embryonic because of epigenetic factors
Date:10/4/2007

A human embryonic stem cell is reined in prevented from giving up its unique characteristics of self-renewal and pluripotency by the presence of a protein modification that stifles any genes that would prematurely instruct the cell to develop into heart or other specialized tissue. But, thanks to the simultaneous presence of different protein modifications, stem cells are primed and poised, ready to develop into specialized body tissue, Singapore scientists reported in last months issue of the journal Cell Stem Cell.

The molecules central to this balancing act, H3K4me3 and H3K27me3, are among the so-called epigenetic modifications that influence the activity patterns of genes in both human embryonic stem (ES) cells and mature human adult cells.

Determining how ES cell genes are modified by these epigenetic markers may explain these cells unique characteristics, said the scientists, who are based at the Genome Institute of Singapore (GIS) and the Bioprocessing Technology Institute (BTI), both under the Agency for Science, Technology and Research (A*STAR), as well as at the National University of Singapore (NUS).

The scientists also discovered that genes modified only by one of the epigenetic markers, H3K4me3, contain the DNA recipes for proteins that enable an ES cell to proliferate, or duplicate itself. In the Cell Stem Cell paper, the scientists wrote, The prevalence of these genes may be related to the self-renewal property of ES cells.

The scientists also found that the genes that do not carry either of the two epigenetic modifications are completely silenced in ES cells. These genes, which are crucial to sensory processes, immunity, and drug metabolism, are active in highly specialized, mature adult cells.

Although epigenetic markers attach themselves to the tightly wound bundle of protein material called histones that package and compress the DNA in the nucleus of each human cell, they do not change the cells DNA code. Therefore, epigenetic markers are not permanent.

If they were permanent, ES cells would never be able to differentiate into heart, kidney, brain, bone, skin and the other specialize cells crucial to normal human functioning.

This discovery will advance our understanding of stem cell epigenetics and chromatin structures, provide potential mechanisms on maintaining the hallmark properties of ES cells, and help researchers with the rich source of information to better understand some of the unique features such as self-renewal and pluripotency of human embryonic stem cells, said Ng Huck Hui, Ph.D., senior group leader at GIS and a member of the Singapore team that conducted this research.

Such findings, Dr. Ng added, will ultimately lead to the development of new therapies and clinical treatments.

His GIS colleague, Wei Chia-Lin, Ph.D., who headed the Singapore research team, said, This study demonstrates the power of a whole genome and robust sequencing technology, when applied in the epigenetic analysis of ES cells, can reveal features of the genomes that were not previously appreciated. The new knowledge and target candidate genes resulted from such unbiased study are ultimately important for researchers to understand the fundamental nature of stem cell proliferation and differentiation.

Drs. Wei and Ng and the other researchers used cutting-edge technologies developed at GIS, to sequence, or decipher, the DNA of human ES cells. With the sequence data in hand, the scientists were able to categorize the genes into three groups, each modified by different combinations of the two epigenetic markers.

The researchers discovered that the majority of the regions in the genome harbor active histone marks that act as sign posts and allow cells to quickly find genes to turn on or activate them.

Identifying the locations of these genomic signposts will also be crucial for discovering human genes that are important for different functions in ES cells.

Of the two epigenetic markers, H3K4me3 was found to be the most prevalent the scientists reported and noted that it occurs near the DNA areas that are promoters of two-thirds of human genes. Of the 17,469 nonredundant unique human genes that the scientists sequenced, 68% contained H3K4me3, and only 10% contained overlapping H3K27me3.

More information about epigenetic modifications:

In living cells, DNA is packaged along with histone proteins, which are chief protein components that act as spools around which DNA winds. The histone proteins are decorated with different marks, which can affect the various activities of the modified DNA such as transcription, gene silencing, imprinting and replication. Such marks key roles in the process of cellular differentiation, allowing cells to maintain different characteristics despite containing the same genomic material. While different cells can have identical genetic DNA sequences, their characteristics and differentiation patterns are influenced by the different marks on the histone proteins. Therefore, histone marks represent an epigenetic marker or code that can be used by the cells to expand their plasticity and complexity.


'/>"/>

Contact: Cathy Yarbrough
sciencematter@yahoo.com
858-243-1814
Agency for Science, Technology and Research (A*STAR), Singapore
Source:Eurekalert

Related biology news :

1. FDA Approves Human Hookworm Vaccine for Phase I Safety Trials
2. Novel technology detects human DNA mutations
3. Current human embryonic stem cell lines contaminated UCSD/Salk team finds
4. UWs Rosetta software to unlock secrets of many human proteins
5. Genome-wide mouse study yields link to human leukemia
6. Found: Missing sequence of the human Y chromosome
7. Study finds more than one-third of human genome regulated by RNA
8. Molecular machine may lead to new drugs to combat human diseases
9. Sea skate experiment sheds light on human cell transport
10. Mouse brain tumors mimic those in human genetic disorder
11. New Clues Add 40,000 Years to Age of Human Species
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/12/2016)... WearablesResearch.com , a brand of Troubadour Research & ... Q1 wave of its quarterly wearables survey. A particular ... a program where they would receive discounts for sharing ... "We were surprised to see that so many ... CEO of Troubadour Research, "primarily because there are segments ...
(Date:4/28/2016)... BANGALORE, India , April 28, 2016 ... of Infosys (NYSE: INFY ), and Samsung SDS, ... partnership that will provide end customers with a more ... payment services.      (Logo: http://photos.prnewswire.com/prnh/20130122/589162 ) ... financial services, but it also plays a fundamental part in ...
(Date:4/26/2016)... -- Research and Markets has announced the ...  report to their offering.  , ,     (Logo: ... forecast the global multimodal biometrics market to grow ... 2016-2020.  Multimodal biometrics is being implemented ... healthcare, BFSI, transportation, automotive, and government for controlling ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... ... June 23, 2016 , ... Mosio, a ... eBook, “Clinical Trials Patient Recruitment and Retention Tips.” Partnering with experienced clinical research ... by providing practical tips, tools, and strategies for clinical researchers. , “The landscape ...
(Date:6/23/2016)... June 23, 2016 /PRNewswire/ - FACIT has announced ... biotechnology company, Propellon Therapeutics Inc. ("Propellon" ... commercialization of a portfolio of first-in-class WDR5 inhibitors ... such as WDR5 represent an exciting class of ... precision medicine for cancer patients. Substantial advances have ...
(Date:6/23/2016)... , ... June 23, 2016 , ... ... YM (Yeast and Mold) microbial test has received AOAC Research Institute approval 061601. ... microbial tests introduced last year,” stated Bob Salter, Vice President of Regulatory and ...
(Date:6/23/2016)... SAN FRANCISCO , June 23, 2016   ... it has secured $1 million in debt financing from ... to ramp up automation and to advance its drug ... for its new facility. "SVB has been ... goes beyond the services a traditional bank would provide," ...
Breaking Biology Technology: