We aim to understand how human embryonic cells adopt different fates as they transit from pluripotency to lineage commitment, and exploit this knowledge for regenerative medicine and disease modelling applications. We are focusing particularly on defining the determinants of anteroposterior (A-P) axial identity (i.e. the position cells occupy along the head-tail axis) and how this influences cell fate decision-making in various multipotent progenitors of the central and peripheral nervous system. To address our questions we employ predominantly human pluripotent stem cell (hPSCs) differentiation as an in vitro model of early human embryonic development and utilise protocols we have recently established toward the production of spinal cord progenitors and neural crest cells (the precursors of various specialised cell types including peripheral neurons) that correspond to distinct axial levels. 

Current projects in our lab include:

1) Understanding how various cellular components of the trunk (e.g. motor neurons, paraxial mesoderm, trunk neural crest) are derived from multipotent axial progenitors 

2) Defining the molecular/signalling basis of A-P axial identity acquisition/maintenance in distinct neural cell types

3) Deciphering the molecular/signalling logic of cell fate decisions in vagal neural crest derivatives focusing on the enteric nervous system and the treatment of enteric neuropathies such as Hirschsprung disease.

4) Determining how abnormal trunk neural crest development is linked to the initiation of neuroblastoma, the most common extra-cranial solid tumour of childhood 

 
Key references:
1) Jevans, B., Cooper, F., Fatieieva, Y., Gogolou, A., Kang Y-N., Restuadi, R., Vanden Bergh, P., Adameyko, I., Thapar, N., Andrews, P.,  De Coppi, P., Tsakiridis, A. , McCann, C. (2024) Human enteric nervous system progenitor transplantation restores functional responses in Hirschsprung Disease patient-derived tissue. Gut. 2024 May 30:gutjnl-2023-331532.

2)  Saldana-Guerrero, I.M., Montano-Gutierrez, L., Boswell, K., Hafemeister, C., Pool, E., Shaw, L.E., Stavish, D., Lea, R.A., Wernig-Zorc, S., Bozsaky, E., Fetahu, I.S., Zoescher, P.,  Pötschger, U., Bernkopf, M.,Wenninger-Weinzierl, A., Sturtzel, C., Souilhol, C., Tarelli, S., Shoeb, M.R.,  Bozatzi, P., Rados, M., Guarini, M., Buri, M.C., Weninger, W., Putz, E.M., Huang, M., Ladenstein, R., Andrews, P.W., Barbaric, I., Cresswell, G.D., Bryant, H.E., Distel, M., Chesler, L., Taschner-Mandl, S., Farlik, M., Tsakiridis, A., Halbritter, F. (2024)  A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations. Nat Commun 15(1):3745. doi: 10.1038/s41467-024-47945-7.

3) Gogolou, A., Souilhol, C., Granata, I., Wymeersch, F. J., Manipur, I., Wind, M., Frith, T. J. R., Guarini, M., Bertero, A., Bock, C., Halbritter, H., Takasato, M., Guarracino, M. R., Tsakiridis, A. (2022). Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor. Elife 11:e74263. doi: 10.7554/eLife.74263.

4) 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. 


 
 















 
 







 
 

                                                         








We are grateful to the following funding bodies for their (past and present) support:  BBSRC, MRC, The Royal Society, Children's Cancer and Leukaemia Group/Little Princess Trust, MRC Discovery Medicine North Doctoral Training Partnership, the White Rose Mechanistic Biology Doctoral Training program, Neuroblastoma UK, YCR and the EU Horizon 2020 (FET Proactive – Boosting emerging technologies) program.