Scientists from the Genome Institute of Singapore (GIS), an institute of the Agency for Science, Technology and Research (A*STAR), in collaboration with the Cancer Science Institute of Singapore (CSI), have discovered how the body uses a single communication system to decide the fate of stem cells. The study, published in the scientific journal PLoS Genetics on 23rd June 2011, paves the way for the development of new methods of stem cell therapy with fewer side effects.
Dr Kian Leong Lee and his team of scientists studied how a single signaling system known as the Nodal/Activin pathway tells stem cells what cell type they should eventually become. The pathway is able to specify a wide range of eventual cell types, challenging the current belief that chemical signaling systems are highly specific and only control a limited number of outcomes. This discovery is a major step forward for stem cell therapies and personalised medicine; by exploiting this signaling system, scientists will be able to control the eventual fate of a stem cell by simply adjusting the chemical environment of a cell. This method of controlling stem cell differentiation also avoids modifying the genetic material of the cell, a procedure that might lead to the cells becoming cancerous.
Dr Lee, first author and post-doctoral research fellow at GIS and CSI said, "Many scientists believe that protein and chemical signaling systems have highly specific functions in biology. However, our study demonstrates that the same type of signal can be changed very dramatically to give different instructions. This finding is extremely significant because it paves the way for advanced studies in cell regeneration and tissue repair, which could ultimately lead to its use in personalized medicine, where stem cells from the same patient could be manipulated to make other types of cells that are genetically matched to the donor."
Urban Lendahl, professor of genetics and vice-chairman at the Department of Cell and Molecular Biology at the Karolinska Institutet, Sweden mentioned, "The report by Lee et al represents a truly significant advance in our understanding of how one of the key signaling mechanisms controls stem cell maintenance and differentiation. The authors show that either an increase or decrease in Nodal/Activin signaling leads to exit from the stem cell state in embryonic stem cells. They also take this a step further, by providing a very exciting molecular explanation for this observation. The finding that pSmad2 regulates distinct gene sets at different levels of Nodal/Activin signaling provides new and important insights into the molecular regulation of the stem cell state."
Notes to the Editor:
Research publication:
The research findings described in the press release can be found in the 23rd June 2011 advance online issue of PLoS Genetics under the title "Graded Nodal/Activin Signaling Titrates Conversion of Quantitative Phospho-Smad2 Levels into Qualitative Embryonic Stem Cell Fate Decisions".
Authors: Kian Leong Lee1,2*, Sandy Keat Lim2,3,4*, Yuriy Lvovich Orlov2,5, Le Yau Yit1, Henry Yang6, Lay Teng Ang2, Lorenz Poellinger1,7 , Bing Lim2,8
- Cancer Science Institute of Singapore, National University of Singapore, Singapore
- Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore
- Duke-NUS Graduate Medical School, National University of Singapore, Singapore
- NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore
- Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
- Singapore Immunology Network, Agency for Science, Technology and Research, Singapore
- Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
- Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, USA.
* Equal contribution
About the Genome Institute of Singapore www.gis.a-star.edu.sg
The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has 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 six consortia & centres, 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.
Journal
PLoS Genetics