Professor of Molecular Haematology
Home page: http://hscl.cimr.cam.ac.uk/
Stem Cells, Cancer
Description of research
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 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.
Further details can be found at http://hscl.cimr.cam.ac.uk/.
Keywords: Stem cells, Gene regulation, Genomics
Clinical conditions: Acute Myeloid Leukaemia, Myeloproliferative Neoplasms
Methodologies: Genome scale transcription factor maps (ChIP-Seq), Expression profiling, Bioinformatics, Transcriptional assays, Network modelling
- Pietras EM, Reynaud D, Kang YA, Carlin D, Calero-Nieto FJ, Leavitt AD, Stuart JM, Göttgens B, Passegué E, “Functionally Distinct Subsets of Lineage-Biased Multipotent Progenitors Control Blood Production in Normal and Regenerative Conditions” Cell Stem Cell 2015 Jul 2;17(1):35-46
- Wilson NK, Kent DG, Buettner F, Shehata M, Macaulay IC, Calero-Nieto FJ, Sánchez Castillo M, Oedekoven CA, Diamanti E, Schulte R, Ponting CP, Voet T, Caldas C, Stingl J, Green AR, Theis FJ, Göttgens B, “Combined Single-Cell Functional and Gene Expression Analysis Resolves Heterogeneity within Stem Cell Populations” Cell Stem Cell 2015 Jun 4;16(6):712-24
- Göttgens B, “Regulatory network control of blood stem cells” Blood 2015 Apr 23;125(17):2614-20
- Lau WW, Hannah R, Green AR, Göttgens B, “The JAK-STAT signaling pathway is differentially activated in CALR-positive compared with JAK2V617F-positive ET patients” Blood 2015 Mar 5;125(10):1679-81
- Göttgens B, “Creating cellular diversity through transcription factor competition” EMBO J 2015 Mar 12;34(6):691-3
- Moignard V, Woodhouse S, Haghverdi L, Lilly AJ, Tanaka Y, Wilkinson AC, Buettner F, Macaulay IC, Jawaid W, Diamanti E, Nishikawa S, Piterman N, Kouskoff V, Theis FJ, Fisher J, Göttgens B, “Decoding the regulatory network of early blood development from single-cell gene expression measurements” Nat Biotechnol 2015 Mar;33(3):269-76
- Ng FS, Schütte J, Ruau D, Diamanti E, Hannah R, Kinston SJ, Göttgens B, “Constrained transcription factor spacing is prevalent and important for transcriptional control of mouse blood cells” Nucleic Acids Res 2014 Dec 16;42(22):13513-24
- Ng FS, Calero-Nieto FJ, Göttgens B, “Shared transcription factors contribute to distinct cell fates” Transcription 2014;5(5):e978173
- Sánchez-Castillo M, Ruau D, Wilkinson AC, Ng FS, Hannah R, Diamanti E, Lombard P, Wilson NK, Gottgens B, “CODEX: a next-generation sequencing experiment database for the haematopoietic and embryonic stem cell communities” Nucleic Acids Res 2015 Jan;43(Database issue):D1117-23.
- Wilkinson AC, Kawata VK, Schütte J, Gao X, Antoniou S, Baumann C, Woodhouse S, Hannah R, Tanaka Y, Swiers G, Moignard V, Fisher J, Hidetoshi S, Tijssen MR, de Bruijn MF, Liu P, Göttgens B, “Single-cell analyses of regulatory network perturbations using enhancer-targeting TALEs suggest novel roles for PU.1 during haematopoietic specification” Development 2014 Oct;141(20):4018-30
- Joshi A, Gottgens B, “Concerted bioinformatic analysis of the genome-scale blood transcription factor compendium reveals new control mechanisms” Mol Biosyst 2014 Nov;10(11):2935-41.
- Sive JI, Göttgens B, “Transcriptional network control of normal and leukaemia haematopoiesis” Exp Cell Res 2014 Dec 10;329(2):255-64
- Pooley C, Ruau D, Lombard P, Gottgens B, Joshi A, “TRES predicts transcription control in embryonic stem cells” Bioinformatics 2014 Oct 15;30(20):2983-5
- Calero-Nieto FJ, Ng FS, Wilson NK, Hannah R, Moignard V, Leal-Cervantes AI, Jimenez-Madrid I, Diamanti E, Wernisch L, Göttgens B, “Key regulators control distinct transcriptional programmes in blood progenitor and mast cells” EMBO J 2014 Jun 2;33(11):1212-26
- Moignard V, Macaulay IC, Swiers G, Buettner F, Schütte J, Calero-Nieto FJ, Kinston S, Joshi A, Hannah R, Theis FJ, Jacobsen SE, de Bruijn MFT, Göttgens B “Characterisation of transcriptional networks in blood stem and progenitor cells using high-throughput single cell gene expression analysis” Nature Cell Biology 2013 15: 363-372
- Ruau D., Ng F.S.L., Wilson N.K., Hannah R., Diamanti E., Lombard P., Woodhouse S, Göttgens B “Building an ENCODE style data compendium on a shoestring” Nature Methods 2013 10(10): 926
- Griffiths DS, Li J, Dawson MA, Trotter M, Cheng Y-H, Smith AM, Mansfield W, Liu P, Kouzarides T, Nichols J, Bannister AJ, Green AR, Göttgens B “LIF independent JAK signalling to chromatin in embryonic stem cells uncovered from an adult stem cell disease” Nature Cell Biology 2010 13: 13-21
- Wilson NK, Foster SD, Wang X, Knezevic K, Schütte J, Kaimakis P, Chilarska P, Kinston S, Ouwehand WH, Dzierzak E, Pimanda JE, de Bruijn MF, Göttgens B (2010) “Combinatorial Transcriptional Control in Blood Stem/Progenitor Cells: Genome-wide Analysis of 10 major Transcriptional Regulators” Cell Stem Cell 2010 7(4):532-544