Dr Anestis Tsakiridis
Brief career history
Various studies in different vertebrate organisms have revealed the existence of a bipotent stem cell-like population which drives embryonic axis elongation through the coordinated production of posterior neuroectoderm (PNE) and paraxial mesoderm (PXM), the building blocks of the spinal cord and trunk skeletal muscle/skeleton respectively. In the mouse embryo these Neuromesodermal Progenitors (NMPs) reside in the late primitive streak (PS) area and later the tailbud, sites which exhibit high WNT/FGF signalling activity.
NMPs are marked by the co-expression of the transcription factors (TFs) Brachyury (T(BRA)) and SOX2, which are indicative of a mesodermal and neural character respectively. Apart from being an excellent model for studying the mechanisms underlying cell fate (neuroectoderm vs mesoderm) decision-making, NMPs also comprise an attractive source for generating spinal cord cells and skeletal muscle in vitro. These cell types are currently difficult to derive from pluripotent stem cells (PSCs) probably because conventional directed differentiation protocols are heavily influenced by the idea that mesodermal and neuroectodermal lineages arise from separate precursors and ignore the existence of NMPs. Thus the ability to maintain pure cultures of NMPs in vitro and define the optimal conditions for their differentiation would be highly desirable.
However, the limited availability of micro-dissected embryonic NMPs has been a major obstacle to the study of both their biology and the molecular events driving their differentiation. To address this issue we have recently defined the optimal culture conditions for the induction of functional adherent NMPs from mouse and, importantly, human PSCs (hPSCs) involving treatment with the WNT agonist CHIR99021 (CHIR) and FGF2. Under these conditions, the majority of the resulting cultures consist of T(BRA)+SOX2+ NMPs after 48-72 hours of treatment.
We now aim to use hPSC-derived NMPs as a tractable in vitro system to address the following questions:
Our research employs hPSC culture and differentiation, CRISPR/Cas9-based genome editing, next generation sequencing and high content/live imaging.
Undergraduate and postgraduate taught modules
We welcome speculative applications. Please email your CV and research interests to:
- Economou C, Tsakiridis A, Wymeersch FJ, Gordon-Keylock S, Dewhurst RE, Fisher D, Medvinsky A, Smith AJH & Wilson V (2015) Intrinsic factors and the embryonic environment influence the formation of extragonadal teratomas during gestation. BMC Developmental Biology, 15(1). View this article in WRRO
- Tsakiridis A, Huang Y, Blin G, Skylaki S, Wymeersch F, Osorno R, Economou C, Karagianni E, Zhao S, Lowell S & Wilson V (2015) Distinct Wnt-driven primitive streak-like populations reflect in vivo lineage precursors. Development, 142(4), 809-809.
- 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 Biology, 12(8). View this article in WRRO
- 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(6), 1209-1221. View this article in WRRO
- Huang Y, Osorno R, Tsakiridis A & Wilson V (2012) In Vivo Differentiation Potential of Epiblast Stem Cells Revealed by Chimeric Embryo Formation. Cell Reports, 2(6), 1571-1578.