Journal article
LIF-independent JAK signalling to chromatin in embryonic stem cells uncovered from an adult stem cell disease
DS Griffiths, J Li, MA Dawson, MWB Trotter, YH Cheng, AM Smith, W Mansfield, P Liu, T Kouzarides, J Nichols, AJ Bannister, AR Green, B Göttgens
Nature Cell Biology | NATURE PUBLISHING GROUP | Published : 2011
DOI: 10.1038/ncb2135
Abstract
Activating mutations in the tyrosine kinase Janus kinase 2 (JAK2) cause myeloproliferative neoplasms, clonal blood stem cell disorders with a propensity for leukaemic transformation. Leukaemia inhibitory factor (LIF) signalling through the JAK-signal transducer and activator of transcription (STAT) pathway enables self-renewal of embryonic stem (ES) cells. Here we show that mouse ES cells carrying the human JAK2V617F mutation were able to self-renew in chemically defined conditions without cytokines or small-molecule inhibitors, independently of JAK signalling through the STAT3 or phosphatidylinositol-3-OH kinase pathways. Phosphorylation of histone H3 tyrosine 41 (H3Y41) by JAK2 was recentl..
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Awarded by Cancer Research UK
Funding Acknowledgements
We gratefully acknowledge the assistance of S. Kinston for technical support, M. Anderson and T. Hamilton for 8-cell-stage injections, K. Griffiths and A. Johnston for assistance with statistics, N. Ivanova for the Nanog shRNA vector, S. Pollard for use of Incucyte, A. Smith for STAT3-null and Nanog-overexpressing ES cells and for helpful discussions and A. Bradley for helpful discussions. Research in the authors' laboratories is supported by Cancer Research UK, Leukaemia and Lymphoma Research, The Leukaemia and Lymphoma Society and Medical Research Council.