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José Silva

Biology of induced pluripotency

The aim of our lab is to understand the underlying biology of the conversion of a somatic epigenome back into a pluripotent epigenome, a process known as induced pluripotency. We are particularly interested in determining the molecular mechanisms by which the key players in this process work. Fully understanding induced pluripotency and better characterising iPS and ES cells is indispensible before these can be used in biomedical applications.

Lab members: Yael Costa, Aliaksandra Radzisheuskaya, Lawrence Bates, Moyra Lawrence, Rodrigo Santos, Hannah Stuart


Key publications:

1. Santos R, Tosti L, Radzisheuskaya A, Caballero I, Kaji K, Hendrich B, Silva JCR. Mbd3/NuRD facilitates induced pluripotency in a context dependent manner. Cell Stem Cell (2014). doi:10.1016/j.stem.2014.04.019

2. Stuart HT, van Oosten AL, Radzisheuskaya A, Martello G, Miller A, Dietmann S, Nichols J, Silva JCR. NANOG amplifies STAT3 activation and they synergistically induce the naïve pluripotent program. Current Biology. (2014). 24, 1–7, February 3 doi: 10.1016/j.cub.2013.12.040.

3. Radzisheuskaya A, Silva JCR. Do all roads lead to Oct4? The emerging concepts of induced pluripotency. Trends in Cell Biology. (2013) Dec 23. pii: S0962-8924(13)00223-7. doi: 10.1016/j.tcb.2013.11.010.

4. Radzisheuskaya A, Chia GLB, Santos R, Theunissen TW, Castro LFC, Nichols J, Silva JCR. A defined Oct4 level governs cell state transitions of pluripotency entry and differentiation into all embryonic lineages. Nature Cell Biology. 30 April (2013) doi:10.1038/ncb2742.

5. Costa Y, Ding J, Theunissen TW, Faiola F, Hore TA, Shliaha PV, Fidalgo M, Saunders A, Lawrence M, Dietmann S, Das S ,Levasseur DN, Li Z, Xu M, Reik W, Wang J#, Silva JCR#. Nanog-dependent function of Tet1 and Tet2 in establishment of pluripotency. Nature. (2013) doi:10.1038/nature11925.

6. Radzisheuskaya A, Pasque V, Gillich A, Halley-Stott RP, Panamarova M, Zernicka-Goetz M, Surani MA, Silva JCR. Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency. Journal of Cell Science. (2012) Oct 17, doi: 10.1242/jcs.113019

7. van Oosten AL, Costa Y, Smith A, Silva JCR. Jak/Stat3 signalling is sufficient and dominant over antagonistic cues for the establishment of naïve pluripotency. Nature Communications. (2012) May 8;3:817. doi: 10.1038/ncomms1822.

8. Theunissen TW, Costa Y, Radzhisheuskaya A, van Oosten AL, Lavial F, Pain B, CastroLFC, Silva JCR. Reprogramming capacity of Nanog is functionally conserved in vertebrates and resides in a unique homeodomain. Development. (2011) Nov;138(22):4853-65.

9. Theunissen TW, van Oosten AL, Castelo-Branco, G Hall J, Smith A, Silva JCR. Nanog overcomes reprogramming barriers and induces pluripotency in minimal conditions. Current Biology. (2011) Jan 11;21(1):65-71. Epub 2010 Dec 30.

10. Silva J#, Nichols J, Theunissen TW, Guo G, van Oosten AL, Barrandon O, Wray J,Chambers I, Yamanaka S, Smith A#. Nanog is the Gateway to the Pluripotent Ground State. Cell. (2009) Aug 21;138(4):722-37

11. Silva J#, Barrandon O, Nichols J, Theunissen T, Kawaguchi J, Smith A#. Promotion of Reprogramming to Ground State Pluripotency by Signal Inhibition. PLoS Biology. (2008) 6(10): e253 doi:10.1371/journal. pbio.0060253.


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