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LINE-1 ACTIVITY IN SOMATIC STEM CELLS: IMPACT AND GENOMIC MOSAICISM

Objective

45% of the human genome is made of repeated DNA, and some types can be mobilized within the genome (mobile DNA). LINE-1 or L1 is the only autonomous active mobile DNA within the human genome, with 500.000 copies per haploid genome (~17% of the genome). Overall, L1 is responsible for ~30% of our genome. Due to its activity and number in the genome, the impact that L1 has and have on the genome is notable. L1 mobility can result in several human diseases (due to insertions within genes) and can also participate in gene creation. L1 mobility is an active process in the human population, and we have recently demonstrated that human embryonic stem cells (hESCs) express L1 and can accumulate new copies of L1. As a result, some of these new copies will be transmitted to newborn individuals. Recently, it has been demonstrated that L1 is active in several somatic adult cell types. These are by definition cell types that will not disperse new L1 copies in the population. As a consequence, these results are a paradigm for the notion of L1 as a piece of “selfish DNA”, which is in the genome solely by its ability to replicate within the genome. In the present application, we will determine the level of expression and activity of L1 elements in several somatic stem cell types (neuronal, mesenchymals, and hematopoietic) in order to inspect the impact and mosaicism generated by L1 in somatic human tissues. The determination of the somatic impact of LINE-1 will shed light in several biological processes: from its role in the Central Nervous System, to its implication in several human diseases (is LINE-1 involved in the progression of human diseases as cancer?). Furthermore, its study will allow the design of therapeutic approaches in order to control its activity in somatic tissues. It is worth mentioning that the somatic activity of LINE-1 could be involved in several human diseases.

Field of science

  • /medical and health sciences/medical biotechnology/cells technologies/stem cells
  • /medical and health sciences/clinical medicine/oncology/cancer
  • /natural sciences/biological sciences/genetics and heredity/genome

Call for proposal

FP7-PEOPLE-2007-4-3-IRG
See other projects for this call

Funding Scheme

MC-IRG - International Re-integration Grants (IRG)

Coordinator

FUNDACION PUBLICA ANDALUZA PROGRESO Y SALUD
Address
Avenida Americo Vespucio 15 Edif S2
41092 Sevilla
Spain
Activity type
Research Organisations
EU contribution
€ 100 000
Administrative Contact
Virginia Nieto Guerrero (Ms.)