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 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 cell types 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.
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Stuart HT, Stirparo G, Lohoff T, Bates L, Kinoshita M, Lim CY, Sousa E, Maskalenka K, Radzisheuskaya A, Malcolm A, Alves MRP, Lloyd R, Nestorowa S, Humpreys 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.
Lawrence M, Theunissen T, Lombard P, Adams D, Silva JCR. ZMYM2 inhibits NANOG mediated reprogramming. Welcome Open Research (2019). Jul 4:88. doi: 10.12688/wellcomeopenres.15250.1.
Sousa EJ, Stuart HT, Bates LE, Ghorbani M, Nichols J, Dietmann S, Silva JCR. Exit from Naive Pluripotency Induces a Transient X Chromosome Inactivation-like State in Males. Cell Stem Cell. (2018) 22(6):919-928. doi:10.1016/j.stem.2018.05.001.
****highlighted in Science: http://science.sciencemag.org/content/360/6396/1417.4
Imogen Stockwell joined the lab as Research Assistant in July 2019.
Do you want to join our Lab?
The Silva Lab welcomes speculative applications from hard-working, highly motivated candidates with a genuine interest in the fundamental biology of nuclear reprogramming. Please address enquiries (include a CV) to firstname.lastname@example.org.
Mariana Alves, summer student in the Silva lab in 2014 (click picture to zoom).