Sheffield Institute for Nucleic Acids

Dr Anestis Tsakiridis

Research interests

We aim to define the molecular basis of cell fate decisions during human embryonic development through the use of human pluripotent stem cells (hPSCs). We focus particularly on the in vitro modelling of the events guiding the “birth” of the spinal cord and trunk musculature from a common precursor population known as Neuromesodermal Progenitors (NMPs) during embryonic axis elongation. We are also interested in another multipotent embryonic progenitor population known as the neural crest (NC). Depending on their position along the anteroposterior (A-P) axis, NC cells give rise to various specialised cell types, such as peripheral neurons, neuroendocrine cells and skeletal cells in the head. We have defined the culture conditions directing  the generation of  NMPs from hPSCs as well as their differentiation into either neural or mesodermal cells (Gouti, Tsakiridis et al., 2014 PloS Biology; Frith et al. 2018 eLife). We have also established efficient protocols for the in vitro production of human NC cells corresponding to most A-P levels and found a close link between NMPs and the precursors of trunk NC cells (Frith et al. 2018 eLife).

Using these in vitro systems we are trying to address the following questions:

1) How do embryonic cells proceed from pluripotency to NM bipotency?
2) What are the molecular determinants of NM bipotency and differentiation?
3) How is axial identity shaped and maintained in human embryonic cells?
4) How do “altered” embryonic multipotent states drive tumourigenesis

Our ultimate goal is to exploit the knowledge from addressing the above questions in order to achieve the precise and efficient engineering of NMP- and NC-derived cell types for regenerative medicine and disease-modelling applications.

 

Key references:

1)  Frith, T.J.R., Granata, I., Wind, Stout, E., M., Thompson, O., Neumman, K., Stavish, D., Heath, P.R., Hackland, J.O.S., Ortmann, D., Anastassiadis, K., Gouti, M., Briscoe, J., Wilson, V., Johnson, SL., Placzek, M., Guarracino, M.R., Andrews, P.W.A., Tsakiridis, A. (2018). Human axial progenitors generate trunk neural crest cells in vitro. Elife. 2018 Aug 10;7. pii: e35786. doi: 10.7554/eLife.35786. [Epub ahead of print].
 
2) Gouti, M*., Tsakiridis, A*., Wymeersch, F., 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 Biology. Aug 26;12(8):e1001937. doi: 10.1371/journal.pbio.1001937. eCollection 2014 Aug.

*joint first authors