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Bertie Göttgens

Transcriptional control of normal and leukaemic blood stem cells

The long term research goal of the Göttgens group is to decipher the molecular hierarchy of regulatory networks responsible for blood stem cell and endothelial development. To this end, the group uses complementary state-of-the-art approaches including embryonic stem cell and transgenic assays, bioinformatics, high throughput sequencing, single cell expression profiling and mathematical modelling. The cumulative output of more than 50 research papers over the last 5 years has been the development of the most comprehensive network model for any adult stem cell type with over 40 transcription factors and more than 100 in vivo validated direct functional interactions.

This integrated approach has resulted in the discovery of previously unrecognised combinatorial interactions between key regulators of blood stem cells with important implications for the transcriptional control of stem cell development and differentiation.

The importance of transcriptional control in both normal and leukaemic cells is underlined by the large number of transcription factor genes that cause leukaemia when disrupted or mutated. Future work will address how transcriptional programmes are perturbed in specific subtypes of leukaemia and may thus open up new avenues for the development of targeted therapies.

The Göttgens lab is based solely at CIMR but Professor Göttgens is also a member of the Cambridge Stem Cell Institute.

Key papers

Moignard, V., Macaulay, I.C., Swiers, G., Buettner ,F., Schütte, J., Calero-Nieto, F.J., Kinston, S., Joshi, A., Hannah, R., Theis, F.J., Jacobsen, S.E., de Bruijn, M.F.T. and Göttgens, B. Characterisation of transcriptional networks in blood stem and progenitor cells using high-throughput single cell gene expression analysis. Nature Cell Biol. 15, 363–372 (2013).

Ruau, D., Ng, F.S.L., Wilson, N.K., Hannah, R., Diamanti, E., Lombard, P., Woodhouse, S. and Göttgens, B. Building an ENCODE style data compendium on a shoestring. Nature Methods 10, 926 (2013).

Griffiths, D.S., Li, J., Dawson, M.A., Trotter, M., Cheng, Y.-H., Smith, A.M., Mansfield, W., Liu, P., Kouzarides, T., Nichols, J., Bannister, A.J., Green, A.R. and Göttgens, B. LIF-independent JAK signalling to chromatin in embryonic stem cells uncovered from an adult stem cell disease. Nature Cell Biol. 13, 13–21 (2011).

Wilson, N.K., Foster, S.D., Wang, X., Knezevic, K., Schütte, J., Kaimakis, P., Chilarska, P., Kinston, S., Ouwehand, W.H., Dzierzak, E., Pimanda, J.E., de Bruijn, M.F. and Göttgens, B. Combinatorial Transcriptional Control in Blood Stem/Progenitor Cells: Genome-wide Analysis of 10 major Transcriptional Regulators. Cell Stem Cell 7, 532–544 (2010).

 

Bertie Göttgens

Professor of Molecular Haematology

Department: Haematology

Cambridge Stem Cell Institute

contact: bg200@cam.ac.uk

01223 336 822

Plain English

Blood stem cells provide the constant supply of new blood cells throughout a person’s lifetime. Their transcriptional regulation, i.e. the fine tuning of which genes should be active at any given time, is critical for their normal function. Moreover, a large number of leukaemias arise when this fine balance of gene activities is disturbed. Transcription factors are genes responsible for controlling the activity of other genes, and they generally function as components of wider regulatory networks. We use a combination of experimental and computational approaches to study transcriptional regulatory networks in blood stem cells, to discover how transcription factor networks control the function of blood stem cells and identify how perturbations of such networks can cause leukaemia.

Group members

Fernando Calero · Lila Diamanti · Debbie Goode · Rebecca Hannah · Isabel Jimenez · Sarah Kinston · Winnie Lau · Ana Leal Cervantes · Vicki Moignard · Felicia Ng · Manuel Sanchez Castillo · Judith Schütte · Jonathan Sive · Yosuke Tanaka · Maggie Wang · Adam Wilkinson · Nicola Wilson · Steven Woodhouse

Funding

BBSRC

Medical Research Council

Leukaemia and Lymphoma Research

Cancer Research UK

Leukaemia and Lymphoma Society

Microsoft Research

NIHR