PLURIPOTENCY

A new model for study relationship between pluripotency and tumorogenesis: molecular insights from basal chordates

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 Obiettivo del progetto (Objective)

'The potential formation of teratoma/teratocarcinoma from pluripotent stem cells represents one the main obstacles to safe use stem cell-based regenerative therapy. The gene network that regulates the stem cell tumoreginicity is still largely unknown. In this study we use as model the chordate Botryllus schlosseri (Ascidiacea), wherein through a process known as vascular budding, an adult is regenerated from pluripotent cells in a sequence of morphologically abnormal developmental stages which pass through a teratoma structure. The teratoma maintains a population of cells that preserve their pluripotency and eventually re-gain positional identity and differentiate “correctly” into a functional body. In this proposed project we take advantage of this in vivo phenomenon to explore the molecular bases regulating the equilibrium between pluripotency and tumorigenicity. We propose two complementary approaches: (1) To undertake unbiased high-throughout gene screening in order to define the trascriptome implicated in the vascular budding (2) to target candidate genes involved in endomesoderm specification and characterize their spatio-temporal patterns of expression and test their functions.'

Introduzione (Teaser)

A European study is pursuing an interesting approach for studying pluripotency and carcinogenesis. By investigating the developmental pathways of a novel model organism, researchers hope to unveil the relationship between these two processes.

Descrizione progetto (Article)

Pluripotent stem cells have the ability to differentiate into many cell types, thereby comprising an attractive cell source for regenerative therapy. However, so far transplantation of these cells in vivo has been characterised by teratoma (encapsulated tumour) formation and an inability to differentiate to the tissue of interest. In order to understand why teratomas form, the EU-funded PLURIPOTENCY project has decided to study the chordate Botryllus schlosseri.

Botryllus schlosseri has been chosen as a model organism as it has the unique capacity to regenerate its body from pluripotent cells through a teratoma-like intermediate. During vascular budding, abnormal developmental stages occur where pluripotent cells are maintained and eventually regain positional identity and differentiate 'correctly' into a functional body. This latter process is termed blastogenesis.

PLURIPOTENCY researchers are confident that by studying this chordate, they will extract important information that could be extrapolated to human pluripotent stem cells. To this end, they plan to analyse gene expression during vascular budding and blastogenesis and to identify candidate genes involved in the maintenance of pluripotency and cell differentiation. So far, scientists have selected 30 candidate genes implicated in either 'stemness', differentiation or cell fate determination.

Botryllus schlosseri has proved an ideal model organism for uncovering evolutionarily conserved basic molecular mechanisms that regulate cell fate in a non-embryonic context. Identifying differences between pluripotent stem cells forming a teratoma and differentiating correctly will give insight into the in vivo behaviour of transplanted teratoma-forming stem cells.