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Genome Institute of Singapore Scientists Discover Molecular Communication Network in Human Stem Cells

July 2, 2013 - Singapore

Scientists at A*STAR's Genome Institute of Singapore (GIS) and the Max Planck Institute for Molecular Genetics (MPIMG) in Berlin (Germany) have discovered a molecular network in human embryonic stem cells (hESCs) that integrates cell communication signals to keep the cell in its stem cell state. These findings were reported in the June 2013 issue of Molecular Cell.

Human embryonic stem cells have the remarkable property that they can form all human cell types. Scientists around the world study these cells to be able to use them for medical applications in the future. Many factors are required for stem cells to keep their special state, amongst others the use of cell communication pathways.

Cell communication is of key importance in multicellular organisms. For example, the coordinated development of tissues in the embryo to become any specific organ requires that cells receive signals and respond accordingly. If there are errors in the signals, the cell will respond differently, possibly leading to diseases such as cancer. The communication signals which are used in hESCs activate a chain of reactions (called the extracellular regulated kinase (ERK) pathway) within each cell, causing the cell to respond by activating genetic information.

Scientists at the GIS and MPIMG studied which genetic information is activated in the cell, and thereby discovered a network for molecular communication in hESCs. They mapped the kinase interactions across the entire genome, and discovered that ERK2, a protein that belongs to the ERK signaling family, targets important sites such as non-coding genes and histones, cell cycle, metabolism and also stem cell-specific genes.

The ERK signaling pathway involves an additional protein, ELK1 which interacts with ERK2 to activate the genetic information. Interestingly, the team also discovered that ELK1 has a second, totally opposite function. At genomic sites which are not targeted by ERK signaling, ELK1 silences genetic information, thereby keeping the cell in its undifferentiated state. The authors propose a model that integrates this bi-directional control to keep the cell in the stem cell state.

These findings are particularly relevant for stem cell research, but they might also help research in other related fields.

First author Dr Jonathan Goke from Stem Cell and Developmental Biology at the GIS said, "The ERK signaling pathway has been known for many years, but this is the first time we are able to see the full spectrum of the response in the genome of stem cells. We have found many biological processes that are associated with this signaling pathway, but we also found new and unexpected patterns such as this dual mode of ELK1. It will be interesting to see how this communication network changes in other cells, tissues, or in disease."

"A remarkable feature of this study is, how the information was extracted by computational means from the experimental data," said Prof Martin Vingron from MPIMG and co-author of this study.

Prof Ng Huck Hui added, "This is an important study because it describes the cell's signaling networks and its integration into the general regulatory network. Understanding the biology of embryonic stem cells is a first step to understanding the capabilities and caveats of stem cells in future medical applications."

Notes to the Editor:

Research publication
The research findings described in the press release was published in the June 2013 issue of Molecular Cell under the title "Genome-wide Kinase-Chromatin Interactions Reveal the Regulatory Network of ERK Signaling in Human Embryonic Stem Cells".

Jonathan Goke[1][2], Yun-Shen Chan[1][3][8], Junli Yan[4][8], Martin Vingron[2] and Huck-Hui Ng[1][3][5][6][7]*
[1] Gene Regulation Laboratory, Genome Institute of Singapore, Singapore 138672, Singapore
[2] Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin 14195, Germany
[3] Graduate School for Integrative Sciences & Engineering, National University of Singapore, Singapore 117456, Singapore
[4] Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
[5] Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore
[6] School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
[7] Department of Biochemistry, National University of Singapore, Singapore 117597, Singapore
[8] These authors contributed equally to this work
* Correspondence: NG Huck Hui, Tel: +65 6808 8145

About the Genome Institute of Singapore (GIS)

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)

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that fosters world-class scientific research and talent to drive economic growth and transform Singapore into a vibrant knowledge-based and innovation driven economy. In line with its mission-oriented mandate, A*STAR spearheads research and development in fields that are essential to growing Singapore's manufacturing sector and catalysing new growth industries. A*STAR supports these economic clusters by providing intellectual, human and industrial capital to its partners in industry. A*STAR oversees 20 biomedical sciences and physical sciences and engineering research entities, located in Biopolis and Fusionopolis as well as their vicinity. These two R&D hubs house a bustling and diverse community of local and international research scientists and engineers from A*STAR's research entities as well as a growing number of corporate laboratories.

About the Max Planck Institute for Molecular Genetics (MPIMG)

The Max Planck Institute for Molecular Genetics (MPIMG) in Berlin, Germany, is one of the leading genome research centres in Europe and belongs to the largest research institutes within the Max Planck Society for the Advancement of Sciences. It comprises four departments, an independent research group as well as a number of independent junior research groups ("Otto Warburg-Laboratory"). Research at the MPIMG concentrates on genome analysis of man and other organisms to contribute to a global understanding of many of the biological processes in the organism, and to elucidate the mechanism behind many human diseases. It is the overall goal of the combined efforts of all MPIMG's groups to gain new insights into the development of diseases on a molecular level, thus contributing to the development of cause-related new medical treatments.


Winnie Lim
Genome Institute of Singapore
Office of Corporate Communications
Tel: +65 6808 8013

Patricia Marquardt
Max Planck Institute for Molecular Genetics
Press and Public Relations
Tel.: +49 30 8413 1716

Source: A*STAR

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