Professor Smith is the Director of the Wellcome Trust/MRC Stem Cell Institute.
The main objective of this group is to characterise the cellular and molecular mechanisms governing the self-renewal and differentiation of multipotential embryo stem cells, of mouse, rat and human origin. Stem cells are defined by the ability both to produce identical daughter cells (self-renewal), and to produce progeny with more restricted fates (commitment and differentiation). This property of stem cells underpins growth and diversification during development and sustains homeostasis and repair processes throughout adult life. An understanding of molecular mechanisms which govern stem cell fate is therefore of fundamental significance in cell and developmental biology and the capabilities arising from such knowledge have major biomedical applications. Embryonic stem (ES) cells, which are derived directly from the pluripotential cells of the earlymouse embryo, can be propagated and manipulated in vitro whilst retaining their full potential for multi-lineage development. Our strategy is to exploit these prototypic stem cell cultures for the identification and characterisation of key regulatory molecules, to determine the significance of these molecules in vitro and in vivo, and thence to develop improved methods of stem cell propagation and manipulation.
Lab members: Nicholas Bredenkamp, Yaoyao Chen, James Clarke, Rosalind Drumond, Ge Guo, Tuzer Kalkan, Aljona Kolmogorova, Masaki Kinoshita, Meng Amy Li, Samuel Myers, Isabelle Nett, Yasmin Paterson, Mariya Rostovskaya, Stanley Strawbridge,
Defining an essential transcription factor program for naïve pluripotency. Dunn SJ, Martello G, Yordanov B, Emmott S, Smith AG. Science. (2014) Jun 6;344(6188):1156-60. doi: 10.1126/science.1248882. PMID: 24904165
Genetic exploration of the exit from self-renewal using haploid embryonic stem cells. Leeb M, Dietmann S, Paramor M, Niwa H, Smith A. Cell Stem Cell. 2014 Mar 6;14(3):385-93. doi: 10.1016/j.stem.2013.12.008. PMID: 24412312
- Identification of the missing pluripotency mediator downstream of leukaemia inhibitory factor. EMBO Journal 32(19):2561-2574 August 2013
- Exit from pluripotency is gated by intracellular redistribution of the bHLH transcription factor Tfe3. Betschinger J, Smith A (2013) Cell
- Esrrb Is a Pivotal Target of the Gsk3/Tcf3 Axis Regulating Embryonic Stem Cell Self-Renewal. Martello G, Sugimoto T, Diamanti E, Joshi A, Hannah R, Ohtsuka S, Gottgens B, Niwa H, Smith A. (2012) Cell Stem Cell, Volume 11, Issue 4, 491-504, 5 October 2012
- The transcriptional and epigenomic foundations of ground state pluripotency. Marks H, Kalkan T, Menafra R, Denissov S, Jones K, Hofemeister H, Nichols J, Kranz A, Francis Stewart A, Smith A and Stunnenberg HG. (2012) Cell Apr; 149(3):590-604
- Klf4 reverts developmentally programmed restriction of ground state pluripotency. Guo G, Yang J, Nichols J, Hall JS, Eyres I, Mansfield W and Smith AG. (2009) Development Apr; 136(7): 1063-1069
- Capture of authentic embryonic stem cells from rat blastocysts. Buehr M, Meek S, Blair K, Silva J, McLay R, Hall J, Ying Q-L and Smith AG. (2008) . Cell 135: 1287-1298
- The ground state of embryonic stem cell self-renewal. Ying QL, Wray J, Nichols J, Batlle-Morera L, Doble B, Woodgett J, Cohen P. and Smith A. (2008) Nature 453: 519-523