The University of Southampton
Centre for Human Development, Stem Cells and RegenerationResearch themes

Systems Biology of Cell Fate

Regulatory landscape

Stem cells have a crucial role during development, tissue regeneration and healthy homeostatic cell turnover.  Collectively, all stem cells share the ability to self renew and differentiate into various different lineages. Owing to their ability to generate tissue de novo following disease or injury there is widespread hope of developing stem cell-based therapies for various degenerative diseases. However, before such stem cell based therapies can be routinely and safely developed, numerous crucial issues must be addressed. In particular, the extended molecular mechanisms of stem cell fate control have yet to be fully determined. To begin to deconstruct these intrinsically complex regulatory mechanisms it is now common for stem cell studies to combine low throughput experimental techniques with an ever-increasing range of different high-throughput experimental techniques. Consequently, stem cell studies now often produce large amounts of data, and integrating these data into a coherent quantitative picture of cell fate control at the systems level is an important current research challenge. To address this challenge, at Southampton we are taking a multi-disciplinary "systems biology" approach to understanding stem cell fate. 

Instead of focusing on the role of individual genes, proteins or pathways in biological phenomena, our aim is to characterize the ways in which essential molecular parts interact with each other to determine the cell fate changes. In order to do this we are employing experimental techniques alongside theoretical and computational methods. Our inherently collaborative team includes experimentalists  from the school of Medicine (Richard OreffoAli Tavassoili) and computational and mathematical modellers (Ben MacArthur and Colin Please) from the School of Mathematics and Institute for Complex Systems Simulation.

Recent Publications
Simón Méndez-Ferrer,Tatyana V. Michurina, Francesca Ferraro, Amin R. Mazloom, Ben D. MacArthur, Sergio A. Lira, David T. Scadden, Avi Ma'ayan, Grigori N. Enikolopov and Paul S. Frenette, Mesenchymal and haematopoietic stem cells form a unique bone marrow niche, Nature 466, 829-834

Rong Lu, Florian Markowetz, Richard D. Unwin, Jeffrey T. Leek, Edoardo M. Airoldi, Ben D. MacArthur, Alexander Lachmann, Roye Rozov, Avi Ma'ayan, Laurie A. Boyer, Olga G. Troyanskaya, Anthony D. Whetton and Ihor R. Lemischka, Systems-level dynamic analyses of fate change in murine embryonic stem cells, Nature 462, 358-362 (2009) 

Ben D. MacArthur, Alexander Lachmann and Avi Ma'ayan, GATE: software for the analysis and visualization of high-dimensional time-series expression data, Bioinformatics 26, 143-144 (2010)

Ben D. MacArthur, Avi Ma'ayan and Ihor R. Lemischka, Systems biology of stem cell fate and cellular reprogramming, Nature Reviews Molecular Cell Biology, 10, 672-681 (2009) 

Ben D. MacArthur, Avi Ma'ayan and Ihor R. Lemischka, Toward stem cell systems biology: from molecules to networks and landscapes, Cold Spring Harbor Symposia on Quantitative Biology 73, 211-215 (2008) 

Ben D. MacArthur, Colin P. Please and Richard O. C. Oreffo, Stochasticity and the molecular mechanisms of induced pluripotency, PLoS ONE 3(8):e3086 (2008)

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