Dr Jennifer Nichols
Collaborators: •Anne Cooke, Department of Pathology, Cambridge •Kay Elder, Bourn Hall Fertility Clinic, Cambridgeshire •Alfonso Martinez-Arias, Department of Genetics, Cambridge •Berenika Plusa, University of Manchester •Joshua Brickman, University of Edinburgh • Jose Silva, WTCSCR, Cambridge • Austin Smith, WTCSCR, Cambridge
Jenny Nichols began her research career with Professor Richard Gardner at the University of Oxford, where she developed a fascination for early mammalian development. She subsequently moved to Edinburgh to join Austin Smith in his newly formed group at the Centre for Genome Research to focus on investigating how the epiblast lineage is established in the embryo and how pluripotent cells can be captured and propagated efficiently in culture as embryonic stem cell lines.
She obtained her PhD in Edinburgh in 1995 and continued as a post doctoral research fellow in Austin Smith's lab until 2006, when she moved to Cambridge to become a group leader under the direction of Professor Smith at the CSCR.
Unlike most other model organisms, the early mammalian embryo possesses an amazing capacity to regulate its own development. Murine embryos develop a pluripotent epiblast at the late blastocyst stage, which can be propagated in vitro in the form of embryonic stem (ES) cells. The first ES cells were derived directly from mouse blastocysts using culture medium supplemented with serum and a 'feeder layer' of mitotically inactivated fibroblasts. The process by which ES cells emerge was not understood, but their potential applications were immediately realised to be enormous. The purpose of our research is to try to understand how the pluripotent cells are assigned and maintained in the embryo; how they can be harnessed and propagated in culture as ES cell lines and how the process of ES cell derivation can be controlled and improved. Addition of selected inhibitors to the culture medium has obviated the requirement for exogenous cytokines for the maintenance and derivation of murine ES cells, apparently by simply removing the option to differentiate. ES cells can be very efficiently derived from mouse and rat embryos cultured in these conditions from the 8 cell stage. This efficiency is apparently attributable to the ability of the inhibitors both to prevent hypoblast differentiation and to promote expansion of the epiblast. We have applied this technology to derive ES cells efficiently from hitherto recalcitrant strains of mice, including non-obese diabetic (NOD) mice.
Although pluripotent cell lines have been derived from other mammals, these lines differ in many respects from murine ES cells, and are more similar to so called ‘epiblast stem cells’ (EpiSCs) derived from post-implantation mouse embryos. We are interested in how differences in early embryonic development of various mammalian species influence their subsequent behaviour in culture. We aim to develop novel strategies to derive non-rodent ES cell lines with properties similar to those of the mouse.
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- Ying, Q-L., Wray, J., Nichols, J., Batlle-Morera, L., Doble, B., Woodgett, J., Cohen, P. and Smith, A. (2008). The ground state of embryonic stem cell self-renewal. Nature, 453, 519-523
- Batlle-Morera, L., Smith, A. G. and Nichols, J. (2008). Parameters influencing derivation of embryonic stem cells from murine embryos. Genesis 46, 758-767
- Nichols, J., Jones, K., Phillips, J. M., Newland, S. A., Roode, M., Mansfield, W., Smith, A. and Cooke, A. (2009). Validated germline-competent embryonic stem cells from nonobese diabetic mice. Nat Med 15, 814-8
- Silva, J., Nichols, J., Theunissen, T. W., Guo, G., van Oosten, A. L., Barrandon, O., Wray, J., Yamanaka, S., Chambers, I. and Smith, A. (in press). Nanog is the gateway to the pluripotent ground state. Cell. 138, 722-737
- Nichols, J., Silva, J., Roode, M. and Smith, A. 2009. Suppression of Erk signalling promotes ground state pluripotency in the mouse embryo. Development 136, 3215-3222