Dr Anestis Tsakiridis

Welcome to the laboratory of Dr Anestis Tsakiridis.

Our group aims 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.  

Neurons


Research

Our research focuses 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 various levels of the A-P axis.

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

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

Funding: The University of Sheffield,  Biotechnology and Biological Sciences Research Council (BBSRC), The Royal Society, Children's Cancer and Leukaemia Group/Little Princess Trust, EU Horizon2020, MRC, Neuroblastoma UK.

Publications

  1. Frith, T.J.R*, Gogolou, A., Hackland, J.O.S., Barbacic, I., Thapar, N., Burns, A., Andrews, P.W.A., Tsakiridis, A*., McCann, C*. Retinoic acid accelerates the specification of enteric neural progenitors from in vitro-derived neural crest. bioRxiv. DOI: https://doi.org/10.1101/819748
  2. Frith, T.J.R. & Tsakiridis, A. (2019). Efficient generation of trunk neural crest and sympathetic neurons from human pluripotent stem cells via a neuromesodermal axial progenitor intermediate. Curr Protoc Stem Cell Biol. 2019 Jan 28:e81. doi: 10.1002/cpsc.81. [Epub ahead of print]
  3. Sutherland, L., Ruhe, M., Gattegno-Ho, D., Mann, K., Greaves, J., Koscielniak, M., Meek, S., Lu, Z., Waterfall. M., Taylor, R., Tsakiridis, A., Brown, H., Maciver, S.K., Joshi, A., Clinton, M., Chamberlain, L.H., Smith, A., Burdon, T. LIF-dependent survival of embryonic stem cells is regulated by a novel palmitoylated Gab1 signalling protein. J Cell Sci. 2018 Sep 20;131(18). pii: jcs222257. 
  4. Frith T.J., Granata, I., Wind, M., Stout, E., Thompson, O., Neumann, K., Stavish, D., Heath, P.R., Ortmann, D., Hackland, J.O., Anastassiadis, K., Gouti, M., Briscoe, J., Wilson, V., Johnson, S.L., Placzek, M., Guarracino, M.R., Andrews, P.W., Tsakiridis, A. (2018). Human axial progenitors generate trunk neural crest cells in vitro. Elife. 2018 Aug 10;7. pii: e35786.
  5. Lopez-Yrigoyen, M., Fizanza, A., Cassetta, L., Axton, R.A., Taylor, H., Meseguer-Rippolles, J., Tsakiridis, A., Wilson, V., Hay, D., Pollard, J.W. & Forrester, L.M. (2018). A human iPSC line capable of differentiating into functional macrophages expressing ZsGreen: a tool for the study and in vivo tracking of therapeutic cells. Philos Trans R Soc Lond B Biol Sci. 2018 Jul 5;373(1750). pii: 20170219.
  6. Economou, C*., Tsakiridis, A*, Wymeersch, F., Gordon-Keylock, S., Dewhurst, R. E., Medvinsky, A., Smith, A. J. H. & Wilson, V. (2015).
    Intrinsic factors and the embryonic environment influence the formation of extragonadal teratomas during gestation.
    BMC Dev Biol 15:35
    *joint first authors
  7. Tsakiridis, A* & Wilson, V*. (2015).
    Assessing the bipotency of in vitro-derived neuromesodermal progenitors
    [v2; ref status: indexed, http://f1000r.es/5p3] F1000Research 2015, 4:100 (doi: 10.12688/f1000research.6345.2).
    *joint corresponding authors
  8. 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
  9. Tsakiridis, A*., Huang, Y., Blin, G., Skylaki, S., Wymeersch, F., Osorno, R., Economou, C., Karagianni, E., Zhao, S., Lowell, S. & Wilson, V*. (2014).
    Distinct Wnt-driven primitive streak-like populations reflect in vivo lineage precursors.
    Development 141, 1209-1221 (One of the three most-read Development articles in 2014).
    *joint corresponding authors
  10. Huang, Y., Osorno, R., Tsakiridis, A. & Wilson, V. (2012).
    The in vivo differentiation potential of epiblast stem cells revealed by chimeric embryo formation.
    Cell Reports 2, 1571-1578 (f1000 recommended).
  11. Osorno, R*., Tsakiridis, A*., Wong, F., Cambray, N., Economou, C., Wilkie, R., Blin, G., Scotting, P. J., Chambers, I. & Wilson, V. (2012).
    The developmental dismantling of pluripotency is reversed by ectopic Oct4 expression.
    Development 139, 2288-2298 (f1000 recommended).
    *joint first authors
  12. Brickman, J.M., Tsakiridis, A., To, C. & Stanford, W.L. (2010).
    A wider context for gene trap mutagenesis.
    Methods Enzymol. 477, 271-95.
  13. Tsakiridis, A., Tzouanakou, E., Rahman, A., Colby, D., Axton, R., Chambers, I., Wilson, V., Forrester, L. & Brickman, J.M. (2009).
    Expression-independent gene trap vectors for random and targeted mutagenesis in embryonic stem cells.
    Nucleic Acids Res. 37, e129.
  14. Tsakiridis, A., Alexander, L.M., Gennet, N., Livigni, A., Sanchez-Martin, R.M., Li, M., Bradley, M. & Brickman, J.M. (2009).
    Microsphere-based tracing and molecular delivery in embryonic stem cells.
    Biomaterials 30, 5853-61.
  15. Sanchez-Martin, R.M., Alexander, L.M., Muzerelle, M., Cardenas-Maestre, J.M., Tsakiridis, A., Brickman J.M. & Bradley, M. (2009).
    Microsphere-mediated protein delivery into cells.
    Chembiochem. 10, 1453-6.
  16. Tsakiridis, A., Tzouanacou, E., Larralde, O., Watts, T.M., Wilson, V., Forrester, L. & Brickman, J.M. (2007).
    A novel triple fusion reporter system for use in gene trap mutagenesis.
    Genesis 45, 353-360.
Positions

There are currently no positions available in the lab. However, we always welcome speculative applications. Please email your CV and research interests to a.tsakiridis@sheffield.ac.uk

Members

Anestis Tsakiridis (Group leader)

Anestis TsakiridisAnestis Tsakiridis did his PhD in Lesley Forrester’s laboratory (2002-2006) at the University of Edinburgh focusing on the development of novel gene trap vectors for random inactivation of lineage-specific genes in mouse embryonic stem cells (mESCs).

He then joined Josh Brickman’s group at the Institute for Stem Cell Research in Edinburgh where, in collaboration with Mark Bradley’s Combinatorial Chemistry group, worked on the development of a novel microsphere-based approach for high-throughput delivery of macromolecules into ESCs. In 2009 he switched his focus on the study of early embryonic development by joining the group of Val Wilson (MRC Centre for Regenerative Medicine, Edinburgh).

As part of the Wilson group he defined decreasing Oct4 expression as the major factor contributing to the developmental extinction of post-implantation embryonic pluripotency and demonstrated that ectopic Oct4 reactivation is sufficient to re-instate pluripotency in non-pluripotent somatic cells. He also explored how Wnt signalling acts on pluripotent cells to drive the progressive generation of bipotent primitive streak lineage precursors using mouse epiblast stem cells (mEpiSCs) as an in vitro model of the gastrula stage embryo and showed for the first time that neuromesodermal progenitors (NMPs) can be “captured” in vitro. He expanded this finding by optimizing the culture conditions for the efficient derivation of NMPs from mEpiSCs and, for the first time, human ESCs.

In the summer of 2015 he was awarded a Vice-Chancellor’s Fellowship from the University of Sheffield to start his own research group at the Centre for Stem Cell Biology (CSBC), Biomedical Sciences Department (BMS) in January 2016.

Group members:

Tom Frith (Postdoc)

Matt Wind (PhD student)

Ingrid Maricel Saldana Guerrero (PhD student)

Antigoni Gogolou (PhD student)

Bronwyn Irving (PhD student-jointly with Dr Heiko Wurdak, University of Leeds)

Bethany James (Research Technician)

Sophia Tarelli (Research Technician)

Oliver Bower (Research Technician)