New Method To Create Induced Pluripotent Stem Cells: Protein Transcription Factor Esrrb's New Role In Cell Reprogramming

Main Category: Stem Cell Research
Article Date: 12 Jan 2009 - 4:00 PDT

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The protein - Esrrb - played an essential role in changing differentiated murine cells back to a pluripotent stem cell state, report scientists at the Genome Institute of Singapore (GIS), a research institute under the Agency for Science, Technology and Research (A*STAR), and the National University of Singapore.

The Singapore scientists' discovery of this alternative method for creating induced pluripotent stem (iPS) cells will be published in Nature Cell Biology on Jan. 11, 2009. This is first research paper highlighting Singapore scientists' novel R&D work in the field of cell reprogramming.

Cell reprogramming is a very new scientific field, which began in 2006 when the reprogramming of differentiated cells back to iPS cells was shown to be possible using three transcription factors Oct4, Sox2 and Klf4.

In the Nature Cell Biology paper, the Singapore scientists report that Esrrb could replace one of the key components, Klf4, in the creation of iPS cells.

Singapore Stem Cell Consortium Executive Director Dr. Alan Colman said, "The reprogramming of somatic cells to an ES cell-like state by Japanese scientists using four transcription factors, remains one of the most important and surprising results in stem cell science in the last five years. We still do not understand the process nor the number of other factors involved. We are one step nearer this solution due to the findings released today by Dr. Ng and his co-workers from the Genome Institute of Singapore. By identifying the nuclear receptor, Esrrb, as another component of the reprogramming mechanism, they further cement their reputation as one of the most productive groups in the world in the area of trying to understand how ES cells work."

Dr. Ng Huck Hui, GIS Senior Group Leader and head of the research team that in collaboration with two other GIS groups headed by Drs Thomas Lufkin and Lim Bing conducted the research reported in Nature Cell Biology, said, "It is known that Klf4 could be replaced by other members of the Klf family of proteins to trigger cell reprogramming. Based on this, we hypothesized that there could be other possible alternatives to Klf family. However, the discovery of Esrrb's role is very surprising as it comes from a family of factors that is very different from Klf.

"I am certain there are still many other components that lie undiscovered, awaiting discovery, "Dr. Ng added. "iPS cells hold a lot of potential eventually in clinical research, but before reaching that goal, we need to continue to discover everything we can on how reprogramming occurs and investigate ways to enhance this process."

Dr. Ng's group has been actively involved in stem cell biology, publishing a paper in Nature Cell Biology in 2008 that showed that similar members of the Klf family of transcription factors could trigger cell programming.

"Reprogramming of cells from one type to another is currently one of the most exciting research areas in cell biology," said Dr Lim Bing, co-author and GIS Senior Group Leader. "No doubt, there are going to be many more surprises in the road ahead in this rapidly developing field. We are glad that we are able to contribute our part towards the understanding of the nuts and bolts of this amazing biological phenomenon early in the game. The addition of another piece to the cell reprogramming jigsaw is extremely gratifying."

The research findings described are published in the Jan. 11, 2009 issue of NATURE CELL BIOLOGY in the paper titled, "Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb".

Authors:

Bo Feng,1,7 Jianming Jiang,1,2,7 Petra Kraus,3 Jia-Hui Ng,1 Jian-Chien Dominic Heng,1,2 Yun-Shen Chan,1,2 Lai-Ping Yaw,1 Weiwei Zhang,1,2 Yuin-Han Loh,1,2 Jianyong Han,3 Vinsensius B. Vega,4 Valere Cacheux-Rataboul,5 Bing Lim,3,6 Thomas Lufkin,3 Huck-Hui Ng1,2,8

1. Gene Regulation Laboratory, Genome Institute of Singapore, 60 Biopolis Street, #02-01, Genome Building, Singapore 138672.
2. Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543.
3. Stem Cell and Developmental Biology, Genome Institute of Singapore.
4. Computational and Mathematical Biology, Genome Institute of Singapore.
5. Cancer Biology & Pharmacology, Genome Institute of Singapore.
6. Harvard Institutes of Medicine, Harvard Medical School, Boston, MA 02115, USA.
7. These authors contributed equally to this work.

Agency for Science, Technology and Research (A*STAR)

A*STAR is Singapore's lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore. A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences and Engineering, with a particular focus on fields essential to Singapore's manufacturing industry and new growth industries. It oversees 22 research institutes, consortia and centres, and supports extramural research with the universities, hospital research centres and other local and international partners. At the heart of this knowledge intensive work is human capital. Top local and international scientific talent drive knowledge creation at A*STAR research institutes. The agency also sends scholars for undergraduate, graduate and post-doctoral training in the best universities, a reflection of the high priority A*STAR places on nurturing the next generation of scientific talent.

The Genome Institute of Singapore (GIS) is a member of A*STAR. It is a national initiative with a global vision that seeks to use genomic sciences to improve public health and public prosperity. Established in 2001 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards the goal of individualized medicine. The key research areas at the GIS include Systems Biology, Stem Cell & Developmental Biology, Cancer Biology & Pharmacology, Human Genetics, Infectious Diseases, Genomic Technologies, and Computational & Mathematical Biology. The genomics infrastructure at the GIS is utilized to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

Genome Institute of Singapore

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