James Briscoe: Projects

In vitro generation of spinal cord cells from ES cells

Stem cells are providing insight into embryo development and offering new approaches to clinical and therapeutic research. In part this progress arises from 'directed differentiation' - artificially controlling the types of cells produced from stem cells. We have developed methods for the directed differentiation of mouse and human embryonic stem cells into cells of the spinal cord and paraxial mesoderm (the tissue that generates muscle and bone that is normally found adjacent to the spinal cord). During normal embryo development, spinal cord and paraxial mesoderm arise from a shared group of precursors known as neuromesodermal progenitors (NMPs). We found that the same combination of signals to which NMPs are exposed to in embryos can be used to generate NMPs from mouse and human pluripotent stem cells. Similar to NMPs in vivo, the in vitro derived NMPs co-express the neural factor Sox2 and the mesodermal factor Brachyury and can be guided into differentiating into either neural or paraxial mesoderm tissue. The neural cells produced from in vitro NMPs have spinal cord but not anterior neural identity and can differentiate into spinal cord motor neurons. The data illustrate how mimicking normal embryonic development allows the generation of specific cell types from ES cells. We are taking advantage of this system to investigate NMPs. We would like to understand how NMPs make the decision between spinal cord and mesoderm and how spinal cord identity is controlled in differentiating cells. In addition this approach provides excellent imaging opportunities to study Shh signalling and gene regulation at single cell resolution.

ESC derived Neuromesodermal Progenitors (NMPs) in vitro and in vivo

ESC derived Neuromesodermal Progenitors (NMPs) in vitro and in vivo

Selected publications

Gouti M, Tsakiridis A, Wymeersch FJ, Huang Y, Kleinjung J, Wilson V, Briscoe J. (2014) In vitro generation of neuromesodermal progenitors reveals distinct roles for Wnt signalling in the specification of spinal cord and paraxial mesoderm identity.     PLoS Biol 12:e1001937

Gouti, M; Metzis, V and Briscoe, J (2015) The route to spinal cord cell types: a tale of signals and switchesTrends in Genetics S0168-9525(15)00039-6

James Briscoe

James Briscoe

james.briscoe@crick.ac.uk
+44 (0)20 379 61388

  • Qualifications and history
  • 1996 PhD Imperial Cancer Research Fund/Kings College, London, UK
  • 1996 Post doctoral fellow Columbia University, New York, USA
  • 2000 Group Leader, Medical Research Council National Institute for Medical Research, London, UK
  • 2015 Group Leader, the Francis Crick Institute, London, UK