Navigation Links
Molecular alliance that sustains embryonic stem cell state
Date:3/4/2008

One of the four ingredients in the genetic recipe that scientists in Japan and the U.S. followed last year to persuade human skin cells to revert to an embryonic stem cell state, is dispensable in ES cells, thanks to the presence of a molecular alliance between a specific group of key proteins known as transcription factors, a research team led by the Genome Institute of Singapore (GIS) under the Agency for Science, Technology and Research (A*STAR) reports in the current issue of Nature Cell Biology.

The reprogramming factor - Klf4, one of the transcription factors that determine whether a cell's genes are active or silent - has at least two other sibling molecules that will substitute Klf4 to maintain a pluripotent embryonic stem (ES) cell state, the GIS-led team said.

Klf4 (also known as gut-enriched Krppel-like factor or Gklf) belongs to the Krppel-like factor (Klf) family of transcription factors that regulate numerous biological processes including proliferation, differentiation, development and apoptosis, or programmed cell death.

Since reprogramming mature cells to the ES state may provide a ready source of tissue for biomedical research and clinical treatment of diseases such as Parkinson's and diabetes, several laboratories, including GIS, are trying to better understand and finely tune the reprogramming process.

The team looks for clues for what these reprogramming ingredients are doing in ES cells.

"Klf4 has been a mysterious player among the four reprogramming factors. As taking out Klf4 in ES cells did not have any apparent effects, it is difficult to reconcile why such a potent reprogramming factor has no role in ES cell biology," said GIS scientist Ng Huck Hui, Ph.D., who headed the research team. Other members of the team include researchers from the National University of Singapore and University of Illinois at Urbana-Champaign.

The GIS research team found that when Klf4 was depleted, Klf2 and Klf5 took over Klf4's role. To understand the molecular basis of the Klf4 redundancy, the scientists studied the DNA binding and transcription activation properties of the three Klfs and found that the profiles of the three Klfs were strikingly similar.

"Most important, the data showed that the other Klfs were bound to the target sites when one of them was depleted." said Dr. Ng. "These Krppel-like factors form a very powerful alliance that work together on regulating common targets. The impact of losing one of them is masked by the other two sibling molecules."

For example, Klfs were found to regulate the Nanog gene and other key genes that must be active for ES cells to be pluripotent, or capable of differentiating into virtually any type of cells. Nanog gene is one of the key pluripotency genes in ES cells.

"We suggest that Nanog and other genes are key effectors for the biological functions of the Klfs in ES cells," Dr. Ng said.

"Together, our study provides new insight into how the core Klf circuitry integrates into the Nanog transcriptional network to specify gene expression unique to ES cells.

The way these factors network with key genes in ES cells suggest a way of how Klf4 (along with the other three reprogramming factors) can jump-start the ES cell gene expression engine in adult cells," he noted.

Although these three Klfs are involved in diverse biological roles, their redundant roles have not been previously appreciated.

"Dr. Ng and his colleagues at the Genome Institute of Singapore again have unraveled another intricacy of what makes a stem cell," said Edison Liu, M.D., Executive Director of GIS. "This work brings us closer to a detailed understanding of the genetic components of stemness."

Alan Colman, Ph.D., internationally recognized leader in stem cell research, said, "Klf4 is a transcription factor that came to prominence recently because it was one of four factors used to reprogram somatic cells back to the pluripotent state seen in embryonic stem cells.

"The mystery of the role of Klf4 has been revealed in studies by Huck Hui and colleagues," added Colman, Executive Director of the Singapore Stem Cell Consortium, which like GIS, is part of Singapore's A*STAR. "They show for the first time that Klf4 itself is not needed for the maintenance of the pluripotent state in ES cells; however, this is because the cells have a number of other Klf-like transcription factors that can substitute for Klf4."


'/>"/>

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

Related medicine news :

1. Sigma-Aldrich Licenses From NeuroSurvival Technologies a Leading Marker for Molecular Imaging of Apoptosis in Vivo
2. Siemens Receives FDA Approval for the VERSANT 440 Molecular System
3. Molecular glue with new effect
4. Story ideas from Molecular and Cellular Proteomics
5. Findings point to molecular Achilles heel for half of breast cancer tumors
6. The Journal of Biomolecular Screening garners Association TRENDS Bronze Award
7. Molecular pathway appears crucial in development of pulmonary fibrosis
8. New book presents comprehensive survey of research into the molecular basis of aging
9. Childrens Hospital researchers identify molecular switch that could save very young lives
10. In the Forefront of Research into Protein Folding and Macromolecular Complex Assembly
11. Cepheid and Broadlane Sign Group Purchasing Contract for GeneXpert(R) Systems and Xpert(TM) Molecular Diagnostic Tests, Including Xpert MRSA
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/8/2016)... ... ... Remember the old saying “rub some dirt on it”? Perhaps you should try ... Clay” the health benefits of integrating clay into a daily diet are numerous, as ... motivational speaker, Perry A~ has since dedicated her life to learning about the benefits ...
(Date:2/8/2016)... , ... February 08, 2016 , ... ... wide variety of organizations. DocuSyst provides a cloud hosted environment for FileHold ... installations include integration with various 3rd party applications using the FileHold web services ...
(Date:2/8/2016)... ... 2016 , ... GrassrootsHealth published data from its D*action public ... in the GrassrootsHealth cohort with substantially higher vitamin D levels than a cohort ... states Carole Baggerly, Director of GrassrootsHealth, “the safety and benefits of vitamin ...
(Date:2/8/2016)... (PRWEB) , ... February 08, 2016 , ... TopConsumerReviews.com recently ... in Mole removal products. , Moles are derived from a cluster of melanin when ... all the wrong places and create a lifetime of embarrassment. Historically, mole removal ...
(Date:2/8/2016)... ... , ... Guruji Mahendra Kumar Trivedi is offering 3 days of accelerated personal ... birthday on February 10th. During this time, people can achieve better health, greater ... people from over 40 different countries as an “ordinary man with an extraordinary gift.” ...
Breaking Medicine News(10 mins):
(Date:2/8/2016)... Feb. 8, 2016  Unilife Corporation ("Unilife" or "Company") (NASDAQ: ... injectable drug delivery systems, today announced that it will release ... December 31, 2015 after market close on February 9, 2016. ... call to discuss these financial results.    About ... --> About Unilife Corporation ...
(Date:2/8/2016)... NORTHBROOK, Ill. , Feb. 8, 2016  Astellas Pharma ... today announced the promotion of James Robinson as ... the company,s operations in North and South America ... president, Astellas Pharma US, representing the commercial organization in ... assumed in 2013. Masao Yoshida , who ...
(Date:2/8/2016)... Palatin Technologies, Inc. (NYSE MKT: PTN), ... for the treatment of diseases with significant unmet ... the United States Patent and Trademark Office (USPTO) ... Patent Application Serial Number 14/313,258 (the ,258 application).  ... female sexual dysfunction using the formulation and dose ...
Breaking Medicine Technology: