Scientists discover gene that improves the quality of reprogrammed stem cells

Scientists from the Genome Institute of Singapore (GIS), a biomedical research institute of the Agency for Science, Technology and Research (A*STAR), have discovered a genetic molecule, called Tbx3, which greatly improves the quality of stem cells that have been reprogrammed from differentiated cells (stem cells reprogrammed from differentiated cells are known as induced pluripotent stem cells or iPS cells). The study was published on 7 February 2010 in the prestigious journal Nature.

Using a series of genomic experiments that examines the process of reprogramming, the scientists discovered that Tbx3 significantly improved the quality of the iPS cells created. Interestingly, this gene is also crucial for many aspects of early developmental processes in mammals. Through the addition of Tbx3 to the existing reprogramming cocktail, the scientists successfully produced better quality iPS cells that were much more efficient in recapitulating the entire developmental process. The capability of iPS cells for germ-line transmission represents one of the most stringent tests of their ESC-like quality. This test requires that iPS cells contribute to the formation of germ cells which are responsible for propagating the next generation of offspring.

Dr George Q. Daley, Director, Stem Cell Transplantation Program, HHMI/Children’s Hospital Boston, Harvard Medical School, added "This paper highlights the rapid progress towards optimized reprogramming strategies. The Singapore group has made an important advance in the production of high quality iPS cells. I would like to congratulate them on this important contribution.”

Embryonic stem cells (ESCs) are undifferentiated master stem cells that are developmentally important because they give rise to all other differentiated cell types in the human body. It has been shown that with the introduction of a few genetic factors into differentiated cells, these master stem (undifferentiated) cells can be re-created through a process known as reprogramming into iPS cells.

Converting adult cells to embryonic cells such as iPS cells represents one of the most astounding breakthrough technologies in biological research. These cells look and behave like normal embryonic stem cells (ESCs) that can generate all other tissue types. Hence the great excitement over iPS potential impact on tissue regeneration and development of therapeutics.

Previous studies have demonstrated how we can make iPS cells by using different cocktails of genetic factors, as well as improve this efficiency via the addition of chemical supplements. However, not all iPS cells generated with different cocktails resemble true ESCs; that is, the quality of the iPS cells is highly varied.

“The ability to produce iPS cells has the potential to accelerate advances in human medicine. To achieve this objective, it is important to establish iPS cells that most closely resemble authentic embryo-derived pluripotent stem cells,” said Prof Azim Surani, professor of physiology and reproduction at the Wellcome Trust /Cancer Research UK Gurdon Institute, University of Cambridge. “The new study by Bing Lim and colleagues shows that the inclusion of Tbx3 as one of the reprogramming factors significantly improves the quality of iPS cells. These iPS cells were superior since viable adults composed entirely of these iPS cells could be generated. These iPS cells also showed superior ability for contribution and transmission through the germ line, which is one of the critical criteria for assessing the quality of iPS cells.”

Dr Lim Bing, Senior Group Leader at the GIS and lead author of the paper said, “This represents a significant milestone in raising the current standards of iPS cell research. With this new knowledge, we are now able to generate iPS cells which are, or approach, the true equivalent of ESCs. When applied to the area of cell therapy-based medicine, we have a better inkling of what we might aim for before differentiating iPS cells to clinically useful cell types. The finding also adds to our insight into the fascinatingly, unchartered but rapidly moving field of reprogramming.”
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Notes to the Editor:

Research publication:

The research findings described in the press release can be found in the 7 February 2010 advance online issue of Nature under the title “Tbx3 improves the germ-line competency of induced pluripotent stem cells”.

Authors:

Jianyong Han1,2, Ping Yuan1, Henry Yang3, Jinqiu Zhang1, Junliang Tay1, Boon Seng Soh1, Pin Li1, Siew Lan Lim1, Suying Cao1, Yuriy L. Orlov4, Thomas Lufkin1, Huck-Hui Ng1,5, Wai-Leong Tam1,*,#, Bing Lim1,6,#

1Stem Cell and Developmental Biology, Genome Institute of Singapore, 138672, Singapore

2State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 10094, China

3Singapore Immunology Network, 138648, Singapore

4Systems Biology, Genome Institute of Singapore, 138672, Singapore

5Department of Biological Sciences, National University of Singapore, 117543, Singapore

6Center for Life Sciences, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA

*Present address: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
#To whom correspondence should be addressed


Stem Cell and Developmental Biology
Genome Institute of Singapore
Genome, #08-01
Singapore 138672
Telephone: 65-6478-8156
Fax: 65-6478-9005
E-mail: tamwl@wi.mit.edu or limb1@gis.a-star.edu.sg

About the Genome Institute of Singapore
www.gis.a-star.edu.sg

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.



About the Agency for Science, Technology and Research (A*STAR)
www.a-star.edu.sg

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.