Dr Jennifer Nichols
Collaborators: Anne Cooke, Department of Pathology, Cambridge • Alfonso Martinez-Arias, Department of Genetics, Cambridge • Berenika Plusa, University of Manchester • Silvia Munoz Descalzo, University of Bath • Ramiro Alberio, University of Nottingham • Paul Bertone, SCI, Cambridge • Kevin Chalut, SCI, Cambridge • Jose Silva, SCI, Cambridge • Austin Smith, SCI, Cambridge
Jenny Nichols began her research career with Professor Richard Gardner at the University of Oxford, where she developed a fascination with early mammalian development. She subsequently moved to Edinburgh to join Professor Austin Smith in his newly formed group at the Centre for Genome Research to investigate 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 as a group leader at the SCI. In October 2014 she became reader of embryonic pluripotency in the Department of Physiology, Development and Neuroscience.
The Nichols group is interested in early mammalian development, in particular, the resolution of lineage decisions and how the embryo accommodates fluctuations in environment, signals and cell number to produce a foetus. The establishment of a population of cells that must protect itself from inappropriate differentiation, whilst retaining the capacity to respond to instructive cues in a timely manner is the main focus. In murine embryos, the naive pluripotent epiblast develops at the late blastocyst stage. Cells with the capacity to produce all adult tissues, including the germ line, can be propagated from the epiblast in vitro in the form of embryonic stem (ES) cells. ES cells can be very efficiently derived from murine embryos cultured in the presence of Erk and GSK3 inhibitors, which both prevent differentiation and promote expansion of the epiblast. Although pluripotent cell lines have been derived from other mammals, these differ from murine ES cells, and are more similar to the primed pluripotent epiblast stem cells derived from post-implantation mouse embryos. We are currently optimising conditions to capture naive pluripotent stem cells from non-rodent mammalian embryos. To understand how pluripotency is acquired and lost in vivo we combine functional, molecular and genetic approaches, utilising mouse embryos with specific and inducible deletions in key pluripotency factors and live imaging of ES cell chimaeras.
- Takashima, Y. Guo, G. Loos, R. Nichols, J. Ficz, G. Krueger, F. Oxley, D. Santos, F. Clarke, J. Mansfield, W. Reik, W. Bertone, P. Smith, A. (2014). Resetting Transcription Factor Control Circuitry toward Ground-State Pluripotency in Human. Cell 158, 1254-69.
- Boroviak T, Loos R, Bertone P, Smith A, and Nichols J (2014). The ability of inner cell mass cells to self-renew as embryonic stem cells is acquired upon epiblast specification. Nat. Cell Biol. 16, 516-28.
- Chia G, Muñoz Descalzo S, Kurowski A, Leitch H, Lou X, Mansfield W, Etienne-Dumeau C, Grabole N, Mulas C, Niwa H, Hadjantonakis A. K, and Nichols J (2014).Oct4 is required for lineage priming in the developing inner cell mass of the mouse blastocyst. Development 141, 1001-10.
- Betschinger J, Nichols J, Dietmann S, Corrin D, Paddison J and Smith A (2013). Exit from pluripotency is gated by intracellular redistribution of the bHLH transcription factor Tfe3. Cell 153, 335-47.
- Roode M, Blair K, Snell P, Elder K, Marchant S, Smith A and Nichols J (2012). Human hypoblast formation is not dependent on FGF signalling. Dev. Biol. 361, 358-63 Faculty 1000 ‘Must read’