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Wellcome - MRC Cambridge Stem Cell Institute



107-Silva-2017Dr José Silva

Reprogramming and programming cell identity


Laboratory: Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre

Departmental Affiliation: Biochemistry                                                         



José received his first degree in Biology from the University of Porto, in Portugal. He joined the GABBA graduate program from University of Porto and then went on to do his PhD studies at Imperial College under the supervision of Professor Neil Brockdorff on heritable silencing mechanisms during mouse development. 

In 2003 and following his PhD, José moved to Professor Austin Smith's laboratory at the University of Edinburgh as an EMBO post-doctoral fellow to investigate factors involved in nuclear reprogramming. This work has led to the identification of Nanog as the first defined gene with nuclear reprogramming capacity in the conversion of a somatic cell into pluripotency. In 2008 José started his own lab at the Cambridge Stem Cell Institute investigating mechanisms of nuclear reprogramming. Currently, José is a Wellcome-Trust Senior Research Fellow. His work has defined roles and mechanisms by which the key drivers of nuclear reprograming work. He is also applying this acquired knowledge into other biological contexts such as X-chromosome-inactivation and stem cell potency.



Wellcome, Medical Research Council (MRC), Biotechnology and Biological Sciences Research Council (BBSRC), Cambridge Trust and Darwin Trust of Edinburgh.


External links

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850 Silva research image 2 1ratio

Panel depicting the appearance of induced pluripotent stem cells (green) from an identified pre-determined to reprogram cell population (red). Non-red cells (grey and blue only) failed to acquire reprogramming competence. (Credit Chibeza Agley) 



Naïve pluripotent stem cells are the cell pillar of development as they give rise to all cell types of the body. My lab research is centered on the understanding of the biology underlying the in vitro generation of naïve pluripotent stem cells via nuclear reprogramming. We then make use of the acquired knowledge to also study the principles governing cell identity change, cell potency, epigenetic regulation and the mechanisms regulating developmental processes taking place in naïve pluripotent stem cells.

Our lines of research are:

1- Understanding the fundamental biology of nuclear reprogramming. Nuclear reprogramming is a fundamental process in biology and also a great model system to study cell identity change. Over the years we have identified some of the key factors in this process and their roles and mechanisms and this remains an important line of research in our lab.

Distinct strategies of reprogramming can be successful at generating induced pluripotent stem cells. These include the use of distinct set of reprogramming drivers. By comparing them we also want to identify and define the principles governing cell identity change during reprogramming.

2- Potential of programing pluripotent stem cells to defined stem cell types of interest. The creation of bonafide pluripotent stem cells from somatic cells by the use of defined factors has opened up the possibility for the generation of any cell type in the petri dish. As a result we are exploring the potential and underlying biology of forward programming pluripotent stem cells into somatic stem cells of interest.  

3- Study the relationship between drivers of reprogramming and epigenetic processes taking place in naïve pluripotent stem cells. Nuclear reprogramming into a naïve pluripotent cell identity involves a radical genomewide transcriptional and epigenetic change. This highlights a potential role of the drivers of nuclear reprogramming regulating these processes. Normal development is somewhat a mirror of reprogramming and we are now asking if the drivers of reprogramming regulate also processes such as the initiation of X-chromosome inactivation which takes place as naïve pluripotent stem cells start to undergo cell differentiation.


 Silva group 2018

Group Members

Lawrence Bates, Aaron Sandoval and Yael Costa


Plain English

Induced pluripotency is a recently discovered way of making cells equivalent to those present in the embryo and with the ability to form all the tissues in the body from adult cells. It involves introducing genes that are normally present in pluripotent cells into adult cells. The aim of our lab is to understand the biology of this process. We believe that this knowledge will bring us closer to using these cells in regenerative medicine and drug discovery.


Key Publications

  • Stuart HT, Stirparo GG, Lohoff T, Bates LE, Kinoshita M, Lim CY, Sousa EJ, Maskalenka K, Radzisheuskaya A, Malcolm AA, Alves MRP, Lloyd RL, Nestorowa S, Humphreys P, Mansfield W, Reik W, Bertone P, Nichols J, Göttgens B, Silva JCR. Distinct molecular trajectories converge to induce naive pluripotency. Cell Stem Cell (2019).  Aug 15. doi: 10.1016/j.stem.2019.07.009.