Link between an epigenetic mark and cell fate restriction during somatic cell differentiation that maintains cell identity and antagonises reprogramming a pluripotent stem cell state. Radzisheuskaya A, Pasque V, Gillich A, Halley-Stott RP, Panamarova M, Zernicka-Goetz M, Surani MA, Silva JCR (2012) Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency. Journal of Cell Science 125: 6094-104. Collaboration between two SCI PIs, Jose Silva and Azim Surani. Selected by the Journal as paper of the year.
Resolution of proliferative stem cell hierarchy in interfollicular epidermis and its dysregulation in the progression from papilloma to squamous cell carcinoma. Mascre G, Dekoninck S, Drogat B, Youssef KK, Brohee S, Sotiropoulou PA, Simons BD, and Blanpain C (2012) Distinct contribution of stem and progenitor cells to epidermal maintenance. Nature 489, 257-62 Driessens G, Beck B, Caauwe A, Simons BD, and Blanpain C (2012) Defining the mode of tumour growth by clonal analysis. Nature 488, 527-30 Collaboration between theoretical group of SCI PI Benjamin Simons and the experimental group of Cedric Blanpain (IRIBHM, Brussels), a member of the SCI ISAB.
Mutated form of the USB1 protein causative for poikiloderma with neutropenia (an inherited leukaemia predisposition disorder affecting the haematopoietic stem cell compartment) disrupts the biogenesis and 3’ end processing of spliceosomal U6 small nuclear RNA. Hilcenko C, Simpson PJ, Finch AJ, Bowler FR, Churcher MJ, Jin L, Packman LC, Shlien A, Campbell P, Kirwan M, Dokal I, Warren AJ (2013) Aberrant 3’ oligoadenylation of spliceosomal U6 small nuclear RNA in poikiloderma with neutropenia. Blood. 121:1028-1038. Epub Nov 2012
Remyelination in the aging mammalian central nervous system by endogenous progenitors, setting the stage for development of phase 1 clinical trial for multiple sclerosis Ruckh JM, Zhao JW, Shadrach JL, van Wijngaarden P, Rao TN, Wagers AJ, Franklin RJ (2012) Rejuvenation of regeneration in the aging central nervous system. Cell Stem Cell 10:96-103 Selected for Best of Cell Stem Cell Collection 2012 In 2012, SCI had active research grants to a value of £12,932,422.76. During the year 17 new grants were awarded to SCI investigators. Of particular note, Benjamin Simons was awarded a Wellcome Trust Senior Investigator Award to start in 2013, Brian Hendrich renewed his Wellcome Trust Senior Research Fellowship and Michaela Frye has been awarded a CRUK Senior Fellowship to start in 2013. In response to our call for junior group leaders, Dr Bon-Kyoung Koo has been recruited from Hans Clevers’ laboratory in Utrecht where among other achievements he identified a new regulatory component of the Wnt pathway in intestinal stem cells (Koo BK et al. Tumour suppressor RNF43 is a stem cell E3 ligase that induces endocytosis of Wnt receptors. Nature 2012 488:665-9). Dr Koo will develop a molecular genetics programme centred on signalling in intestinal stem cells. He will move to Cambridge in April 2013. In addition, as part of our strategy for developing a programme in the physical biology of stem cells, Kevin Chalut, a Royal Society research fellow in the Department of Physics, has joined SCI and will relocate half of his laboratory. Dr Chalut is interested in the role of biomechanics in pluripotent stem cells (Chalut, K., Höpfler, M., Lautenschläger, F., Martinez-Arias, A., and Guck, J. (2012) Chromatin decondensation and nuclear softening accompany Nanog downregulation in embryonic stem cells. Biophysical Journal 103: 2060-2070.) The second Cambridge Stem Cell Institute International Symposium on the theme of “Cancer Stem Cells” was organised by Michaela Frye and Juan Ventura. The meeting was over-subscribed and very well received by those who did attend. The third Symposium on 9/10 July 2013 will be on “Physical Biology of Stem Cells” is being organised by Ben Simons, Alfonso Martinez-Arias and Austin Smith. The Cambridge Stem Cell Club resumed in 2012 providing a valuable networking forum. Meetings have been well attended with talks from a mixture of SCI Group Leaders and post-docs. As part of the Institute’s public engagement programme a set of activities were organised by PhD students for the Cambridge science festival and were well-received. Finally, a rebranded Stem Cell Institute WEB site (www.stemcells.cam.ac.uk) has been created. The site provides resources for both academic and lay audiences and also includes an intranet providing details on core facilities and facilitating exchange of resources between SCI research groups.