Professor Austin Smith
Pluripotent stem cells
Laboratory: Cambridge Stem Cell Institute, Gleeson Building. Departmental Affiliation: Biochemistry
As an undergraduate in Oxford Austin Smith became captivated by pluripotency He pursued this interest through PhD studies in Edinburgh and postdoctoral research back in Oxford. He returned to Edinburgh as a Group Leader in 1990 and from 1996 was Director of the Centre for Genome Research, later the Institute for Stem Cell Research. In 2006 he moved to Cambridge where he was the founding Director of the Stem Cell Institute.
Professor Smith is a Medical Research Council Professor, an EMBO Member, and a Fellow of the Royal Societies of Edinburgh and of London. In 2010 he was awarded the Louis Jeantet Prize and in 2016 he received the ISSCR McEwen award for Innovation.
Isaac Newton Trust, Wellcome Trust, Medical Research Council, University of Sheffield, European Commission, Microsoft Research
We propose that pluripotency may be partitioned into three phases; naïve, formative, and primed. Mouse embryonic stem cells correspond to the naïve stage while post-implantation epiblast stem cells (EpiSCs) represent primed pluripotency. Conventional human pluripotent stem cells are more similar to EpiSCs. Our current research indicates that these human cells can be “reset” to a naïve state and furthermore that naive cells may be captured directly from the human embryo. (Credit – adapted from Smith A. Development 2017 144: 365-373)
We study pluripotent stem cells derived from early embryos or generated by somatic cell reprogramming. These cell lines retain the potential to generate all somatic cell types. Our goal is to understand how pluripotent stem cells maintain broad developmental potency and how they prepare for and make cell fate decisions. Ultimately we aim to control the lineage decision process. We compare pluripotent cells from rodents and primates to elucidate common principles and species-specific adaptations.
Nicholas Bredenkamp, James Clarke, Rosalind Drummond, Ge Guo, Tuzer Kalkan, Masaki Kinoshita, Meng Amy Li, Sam Myers, Mariya Rostovskaya, Stanley Strawbridge.
For PhD opportunities in 2017, please visit the Study section.
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.
- Kalkan T, Olova N, Roode M, Mulas C, Lee HJ, Nett I, Marks H, Walker R, Stunnenberg HG, Lilley KS, Nichols J, Reik W, Bertone P, Smith A. Tracking the embryonic stem cell transition from ground state pluripotency. Development 2017 doi:10.1242/dev.142711 PMID: 28174249
- Smith A. (2017) Formative pluripotency: the executive phase in a developmental continuum. Development 2017 144: 365-373; PMID: 28143843
- Guo G, von Meyenn F, Santos F, Chen Y, Reik W, Bertone P, Smith A, Nichols J. (2016) Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass. Stem Cell Reports. 2016 Apr 12;6(4):437-46 PMCID: PMC4834040
Leeb M, Dietmann S, Paramor M, Niwa H, Smith A. (2014) Genetic exploration of the exit from self-renewal using haploid embryonic stem cells. Cell Stem Cell. 2014 Mar 6;14(3):385-93 PMCID: PMC3995090
Takashima Y, Guo G, Loos R, Nichols J, Ficz G, Krueger F, Oxley D, Santos F, Clarke J, Mansfield W, Reik W, Bertone P, Smith A (2014) Resetting Transcription Factor Control Circuitry toward Ground-State Pluripotency in Human. Cell 158 (6), 1254-1269. PMCID: PMC4162745