In the new issue of the journal Cell Stem Cell, Singapore scientists report the surprising discovery that a novel transcription factor, Nr5a2, can replace one of the classical reprogramming factors, Oct 4, to significantly increase the efficiency of reprogramming differentiated stem cells into induced pluripotent stem cells (iPS cells).
Previous research revealed that the reprogramming of differentiated cells into induced iPS cells could be achieved by the three transcription factors, Oct4, Sox2 and Klf4.
In this latest finding, which is potentially relevant to cell therapy-based medicine, Genome Institute of Singapore (GIS) and National University of Singapore (NUS) scientists determined that Nr5a2 can replace Oct4. Thus, a new combination of Nr5a2, Sox2 and Klf4 can reprogram differentiated cells into iPS cells.
"This is a very exciting moment," said GIS Senior Group Leader Ng Huck Hui, Ph.D. "Fundamental research in embryonic stem cells is extremely important for us to harness the full potentials of these cells, and this study provides valuable and crucial insights into the mechanism of reprogramming.
"Given Oct4's critical role in embryonic stem cells and reprogramming, we were very surprised with the discovery that Nr5a2 could replace Oct4," added Dr. Ng, senior author of the paper. "This study highlights the prospect of finding more surprises in the field of reprogramming."
"This paper represents significant addition to the very active field of cellular reprogramming," added Davor Solter, M.D., Ph.D., Senior Principal Investigator at Singapore's Institute of Medical Biology (IMB).
Both GIS and IMB are part of Singapore's A*STAR (Agency for Science, Technology and Research).
"The authors show that gene coding for nuclear receptor Nr5a2 can replace one of the classical reprogramming factors Oct 4," Dr. Solter said. "In addition they presented evidence that this and another nuclear receptor can significantly increase the efficiency of reprogramming. These results have great basic and practical significance."
The reprogramming of differentiated cells into iPS cells is one of the most important breakthroughs in stem cell research, because iPS cells can give rise to all other differentiated cell types that make up the human body.
Because they behave like embryonic stem cells, iPS cells are important starting points for the creation of organs for replacement or transplantation.
The Cell Stem Cell paper, published on Jan. 21, 2010, is the second research report on iPS cell science by Dr. Ng's research group. In Jan. 2009, Dr. Ng and his colleagues reported in Nature Cell Biology that the transcription factor Esrrb could replace Klf4 in the combination of Oct4, Sox2 and Klf4 for iPS cell creation.
The paper titled, "The Nuclear Receptor Nr5a2 can replace Oct4 in the Reprogramming of Murine Somatic Cells to Pluripotent Cells," will be published in the Jan. 21, 2010 online issue of Cell Stem Cell.
Jian-Chien Dominic Heng,1,2,* Bo Feng,1,* Jianyong Han,3,* Jianming Jiang,1 Petra Kraus,3 Jia-Hui Ng,1,2 Yuriy L. Orlov,4 Mikael Huss,4 Lin Yang,1 Thomas Lufkin,3,6 Bing Lim,3,5 Huck-Hui Ng1,2,6,#
- Gene Regulation Laboratory, Genome Institute of Singapore.
- NUS Graduate School for Integrative Sciences and Engineering, Singapore.
- Stem Cell and Developmental Biology, Genome Institute of Singapore.
- Computational and Systems Biology group, Genome Institute of Singapore.
- Center for Life Sciences, Harvard Medical School, Boston.
- Dept of Biological Sciences, National University of Singapore.
* These authors contributed equally to this work.
# Corresponding author:
Dr. Ng: Telephone (+65) 6478 8145
Genome Institute of Singapore
The Genome Institute of Singapore (GIS) is a member of the Agency for Science, Technology and Research (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.
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The Agency for Science, Technology and Research (A*STAR) is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences, and physical sciences and engineering research institutes, and seven consortia & centre, which are located in Biopolis and Fusionopolis, as well as their immediate vicinity.
A*STAR supports Singapore's key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, hospitals, research centres, and with other local and international partners.
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