Profile Pic 2014

Professor Austin Smith

Stem Cell Potency


Laboratory Location:

Stem Cell Institute, Gleeson Building, Smith Lab Members

Departmental Affiliation:

Department of Biochemistry, University of Cambridge

Tel 01223 (7)60233


Nicholas Bredenkamp • Yaoyao Chen • James ClarkeRosalind DrumondGe GuoTuzer Kalkan Masaki Kinoshita •Meng Amy Li • Samuel Myers  • Meryem RalserMariya Rostovskaya  • Stanley Strawbridge 


Harry Leitch

Personal Information

Professor Austin Smith was captivated by pluripotency and stem cell self-renewal by undergraduate lectures from Professor Chris Graham in Oxford. He pursued this interest through PhD studies with Martin Hooper at the University of Edinburgh from 1982-86. Following postdoctoral research at the University of Oxford with John Heath, he returned to Edinburgh in 1990 as a Group Leader at the Centre for Genome Research. In 1996, he was appointed Director of the Centre, which under his leadership became the first Institute for Stem Cell Research in the United Kingdom. He was awarded an MRC Research Professorship in 2003. In 2006 he moved to the University of Cambridge where he is currently Director of the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute. He coordinated the European Commission integrated project EuroStemCell (2004-2008) and currently coordinates the EuroSyStem project (2008-2012). Professor Smith is a Fellow of the Royal Society of Edinburgh, an elected member of EMBO, and a Fellow of the Royal Society of London. In 2010 he was awarded the Louis Jeantet Prize.

Research Interests:

Our group studies pluripotent stem cells that can be expanded in vitro while retaining the ability to generate all types of cell. Our goal is to understand how pluripotency is generated and to reveal the molecular programme that proceeds into multilineage commitment (see Figure).  We seek to find common principles that underpin pluripotency in different mammalian species. In mouse, stem cells corresponding to the beginning and end states of pluripotency can be captured and propagated. We are currently focussing on determining conditions for obtaining and propagating human stem cells in the initial naïve state analogous to mouse embryonic stem cells. We are also investigating the isolation and stable propagation of cells in the intermediate formative stage of pluripotency. Our long-term goal is to control the growth and differentiation of human pluripotent stem cells to obtain insights into early human embryo development and for applications in drug discovery and regenerative medicine.

Image Brochure 1

Pluripotency can be divided into three phases; naïve, formative, and primed. Mouse embryonic stem cells correspond to naïve pluripotency while post-implantation epiblast stem cells (EpiSCs) represent primed pluripotency. Conventional human pluripotent stem cells are similar to EpiSCs.

Stem cells expanded from the human embryonic hindbrain stably retain regional specification and high neurogenic potency: 


Plain English

In the early embryo a small group of cells acquire the ability to make all cell types of the animal. This property is called pluripotency. It is possible to grow pluripotent cells in the laboratory. These are called embryonic stem cells. Research with mouse embryonic stem cells over the past 10 years has identified the master genes that control pluripotency. However, there is still an important part that we do not understand well; how do the pluripotent cells choose to make different types of tissue? We study this question in mouse, rat and human. An aim of this work is to obtain human embryonic stem cells with well understood properties that can provide a reliable foundation for pharmaceutical research and clinical applications.

Key Publications

  • The Nature of Embryonic Stem Cells. Martello G, Smith A. Annual Review of Cell and Developmental Biology. Vol. 30: 647-675 October 2014
  • Identification of the missing pluripotency mediator downstream of leukaemia inhibitory factor. Martello G, Bertone P, Smith A. EMBO Journal 32(19):2561-2574 August 2013
  • Exit from pluripotency is gated by intracellular redistribution of the bHLH transcription factor Tfe3. Betschinger J, Nichols J, Dietmann S, Corrin PD, Paddison PJ, 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

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