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International Journal of Fertility and Sterility، جلد ۴، شماره ۲-۱، صفحات ۵۴-۵۴
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عنوان انگلیسی I-54: New Models for Human and Mouse Genetic
چکیده انگلیسی مقاله The possibility to reprogram somatic human cells will greatly and deeply change genetic approach and allow the development of new tools to study genetics diseases. Indeed, our ability to study human genetic diseases suffers from the lack of valid in vitro models. The latter should (i) be originating from human primary cells, (ii) be able to self-renew for a long time and (iii) be able to differentiate into a wide range of different tissue types. Human embryonic stem (hES) cells harbour all those properties and may provide a first source for establishing such in vitro models. Alternatively, reprogramming strategies offer a very new possibility to derive induced-pluripotent stem (iPS) cells from clinically described patients or from complex mouse transgenic models. Human ES cells carrying genetic disorders are a promising tool to develop in vitro cellular model for physiopathology investigations and drug screening. This field is actively growing but suffers of the low number of available embryos.Ideally to overcome this limitation, cells derived from patients should be reprogrammed to acquire an ES-like phenotype allowing their amplification in an unaltered state and their in vitro differentiation in a broad variety of phenotypes. In that context, reprogramming adult cells has focused scientific community interest for their potentially inexhaustible source of cells for both therapy replacement and models developments. First publication in 2006, Yamanaka’s team published the reprogramming of mouse fibroblast toward an ES-like phenotype. Authors identified a minimal set of genes, i.e. Oct3/4, Sox2, c-Myc and Klf4 able to successfully reprogram embryonic and adult fibroblasts into ES-like cells. Reprogrammed cells (called iPS cells, for induced-Pluripotent Stem cells) share ES cells markers and capacities.With the goal to develop new models for monogenic diseases, we set up a first program based on hESC derivation from affected preimplantation genetic diagnosis (PGD)-identified embryos So far we have establish 17 hES lines for 10 different pathologies. All the cell lines are banked by our collaborator I-Stem. All our cell lines are registered to the European Human Embryonic Stem Cell Registry and available to the scientific community. This represents one of the most important collections of hES cell lines carrying mutation available for the scientific community. For pathologies not tested by PGD, we implemented somatic cell reprogramming technology to derive iPS from human/mouse fibroblasts. As a first example, we established iPSC from 2 adult patients carrying Friedreich ataxia. Such cells are now under characterisation. In addition, we have establish iPS cell lines from different transgenic mouse lines, which are used now either to study their differentiation properties in vitro or as a tool to decipher pluripotency.
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نشانی اینترنتی http://ijfs.ir/journal/article/abstract/2458
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