Dr Jennifer Nichols
Cambridge Stem Cell Institute, Gleeson Building
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.
BBSRC, Wellcome Trust
Murine embryos develop a pluripotent epiblast by the late blastocyst stage. This tissue is the source of the foetus; it can also be propagated in vitro as embryonic stem (ES) cells. Understanding how the pluripotent lineage is specified, maintained and relinquished during development is critical to establish protocols for efficient capture and controlled differentiation of ES cells in culture. Pluripotent cell lines have been generated from other mammals, but they differ significantly from murine ES cells. To begin to understand the underlying distinctions, we have characterised the ‘naïve’ pluripotent epiblast in mouse embryos in detail. Combining these studies with a recently developed culture regime based upon inhibition of differentiation and polarisation, we have captured and propagated the equivalent naïve state from human embryos. To further our understanding of cell fate decisions in early mouse embryos, we use a combination of genetic modification, ex vivo culture and molecular profiling to investigate the roles of relevant pluripotency factors and signalling pathways. Mouse ES cells can be transplanted into embryos to produce chimaeras. Using labelled ES cells, we can monitor the dynamics of integration and subsequent differentiation. We have shown that ES cells beginning the process of exit from pluripotency are actively eliminated from early host embryos when injected alongside naïve pluripotent ES cells, but can occasionally incorporate into the epiblast in the absence of such competition. Currently, we are using chimaeras to investigate early lineage segregation in the host embryo in response to administration of normal or mutant ES cells.
We are interested in the early embryonic tissue destined to form the foetus, and how stem cell lines that retain the capacity to produce all tissues in the body can be captured from it. Mouse embryonic stem (ES) cells were first derived many years ago. Why similar cell lines were not available from other larger mammals has been the subject of intense study. A culture regime has now been developed that allows capture of equivalent cell lines directly from donated human embryos. We continue to use the mouse embryo and ES cells as a model system to try to understand early mammalian embryonic development, in particular, how tissues are specified and regulated. A powerful tool for this purpose is the ability to make chimaeras by transplanting labelled ES cells into early mouse embryos. We study the potential of both the ES cells and the host embryo in this way.
- Guo G, von Meyenn F, Santos F, Chen Y, Reik W, Bertone P, Smith A, Nichols J (2016). Naïve pluripotent stem cells derived directly fromisolated cells of the human inner cell mass. Stem Cell Reports. 2016 Feb 27. pii: S2213-6711(16)00056-4 PMID:26947977
- Alexandrova S, Kalkan T, Humphreys P, Riddell A, Scognamiglio R, Trumpp A, Nichols J. (2015). Selection and dynamics of embryonic stem cell integration into early mouse embryos. Development 143, 24-34 PMCID: PMC4725202
- 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, Nichols J (2014). Oct4 is required for lineage priming in the developing inner cell mass of the mouse blastocyst. Development 141, 1001-10 PMCID:PMC3929414
- Boroviak T, Loos R, Bertone P, Smith A, Nichols J (2014). The ability of inner cell mass cells to self-renew as embryonic stem cells is acquired upon epiblast specification. T. Nat. Cell Biol. 16, 516-28 PMID:24859004
- Roode M, Blair K, Snell P, Elder K, Marchant S, Smith A, Nichols J (2012). Human hypoblast formation is not dependent on FGF signalling. Dev. Biol. 361, 358-63 PMCID:PMC3368271