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Generation of neurons from somatic cells of healthy individuals and neurological patients through induced pluripotency or direct conversion

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Access to healthy or diseased human neural tissue is a daunting task and represents a barrierfor advancing our understanding about the cellular, genetic, and molecular mechanisms underly-ing neurogenesis and neurodegeneration. Reprogramming of somatic cells to pluripotency bytransient expression of transcription factors was achieved a few years ago. Induced pluripotentstem cells (iPSC) from both healthy individuals and patients suffering from debilitating, life-threatening neurological diseases have been differentiated into several speciﬁc neuronal sub-types. An alternative emerging approach is the direct conversion of somatic cells (i.e., ﬁbro-blasts, blood cells, or glial cells) into neuron-like cells. However, to what extent neuronal directconversion of diseased somatic cells can be achieved remains an open question. Optimizationof current expansion and differentiation approaches is highly demanded to increase the differ-entiation efﬁciency of speciﬁc phenotypes of functional neurons from iPSCs or through somaticcell direct conversion. The realization of the full potential of iPSCs relies on the ability to pre-cisely modify speciﬁc genome sequences. Genome editing technologies including zinc ﬁngernucleases, transcription activator-like effector nucleases, and clustered regularly interspacedshort palindromic repeat/CAS9 RNA-guided nucleases have progressed very fast over the lastyears. The combination of genome-editing strategies and patient-speciﬁc iPSC biology will offera unique platform for in vitro generation of diseased and corrected neural derivatives for per-sonalized therapies, disease modeling and drug screening.

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Articles publicats en revistes (Patologia i Terapèutica Experimental)

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Generation of neurons from somatic cells of healthy individuals and neurological patients through induced pluripotency or direct conversion