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METSTEM

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DNA methylation in stem cells

Embryonic and adult stem cells constitute an important component of biology by providing a pool of pluri- and multi-potent cells that supply a variety of different cell lineages. Little is known about the mechanisms involved in es... ver más

31/03/2016

THE HEBREW UNIVERS...

2M€

Presupuesto del proyecto: 2M€

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THE HEBREW UNIVERSITY OF JERUSALEM No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

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Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2016-03-31 No tenemos la información de la convocatoria

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Líder del proyecto

THE HEBREW UNIVERSITY OF JERUSALEM No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Embryonic and adult stem cells constitute an important component of biology by providing a pool of pluri- and multi-potent cells that supply a variety of different cell lineages. Little is known about the mechanisms involved in establishing and maintaining cell ¿stemness,¿ but it is most likely controlled by epigenetic signals such as DNA methylation. This proposal aims to understand these mechanisms and decipher the molecular logic used to program this plasticity. We have developed a new strategy for studying the ¿DNA methylation potential¿ of any cell type throughout normal development. This utilizes a unique set of transgenic vectors programmed to detect both de novo methylation as well as the ability to protect CpG islands, and will, for the first time, allow one to evaluate the role of demethylation in normal stem cells and during reprogramming. This will be done using a new technique called ¿reverse epigenetics¿. Preliminary studies indicate that embryonic stem cells differentiated in vitro undergo extensive aberrant methylation that does not reflect the normal pattern of methylation found in vivo. This artifact may be responsible for our inability to attain efficient differentiation in culture and may generate cells that are unhealthy and prone to cancer. We will characterize the causes of this phenomenon and decipher its underlying mechanism. This research should lead to the development of improved methods for tissue generation in vitro. One of the most basic properties of adult stem cells is their ability to undergo asymmetric cell division that is often associated with unequal segregation of DNA. This mechanism is one of the most elemental, yet mysterious, aspects of stem cell biology. We have developed a completely new molecular model for this process that is based on the idea that non-symmetric DNA methylation serves as a strand-specific marker, and it is very likely that this will enable us to finally decipher this basic aspect of stem cells.

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