Concise Review: Generation of Neurons From Somatic Cells of Healthy Individuals and Neurological Patients Through Induced Pluripotency or Direct Conversion

Authors

  • Iván Velasco,

    Corresponding author
    1. Instituto de Fisiología Celular-Neurociencias, Universidad Nacional Autónoma de México, México, D.F, México
    2. Centro GENYO, Granada, Spain
    • Correspondence: Pablo Menéndez, Ph.D., MBA, ICREA Research Professor, Josep Carreras Leukaemia Research Institute, Facultat de Medicina, University of Barcelona, Carrer Casanova 143, 08036 Barcelona, Spain. Telephone: +34 93 557 2809; Fax: +34 93 323 1751; e-mail: pmenendez@carrerasresearch.org; or Iván Velasco, Ph.D., Instituto de Fisiología Celular-Neurociencias, Universidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad Universitaria, México, D.F. 04510, México. Telephone: +52 55 5622 5649; Fax: +52 55 5622 5607; e-mail: ivelasco@ifc.unam.mx

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  • Patricia Salazar,

    1. Instituto de Fisiología Celular-Neurociencias, Universidad Nacional Autónoma de México, México, D.F, México
    2. Centro GENYO, Granada, Spain
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  • Alessandra Giorgetti,

    1. Josep Carreras Leukemia Research Institute, Cell Therapy Program, University of Barcelona, Barcelona, Spain
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  • Verónica Ramos-Mejía,

    1. Centro GENYO, Granada, Spain
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  • Julio Castaño,

    1. Josep Carreras Leukemia Research Institute, Cell Therapy Program, University of Barcelona, Barcelona, Spain
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  • Damià Romero-Moya,

    1. Josep Carreras Leukemia Research Institute, Cell Therapy Program, University of Barcelona, Barcelona, Spain
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  • Pablo Menendez

    Corresponding author
    1. Josep Carreras Leukemia Research Institute, Cell Therapy Program, University of Barcelona, Barcelona, Spain
    2. Instituciò Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
    • Correspondence: Pablo Menéndez, Ph.D., MBA, ICREA Research Professor, Josep Carreras Leukaemia Research Institute, Facultat de Medicina, University of Barcelona, Carrer Casanova 143, 08036 Barcelona, Spain. Telephone: +34 93 557 2809; Fax: +34 93 323 1751; e-mail: pmenendez@carrerasresearch.org; or Iván Velasco, Ph.D., Instituto de Fisiología Celular-Neurociencias, Universidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad Universitaria, México, D.F. 04510, México. Telephone: +52 55 5622 5649; Fax: +52 55 5622 5607; e-mail: ivelasco@ifc.unam.mx

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Abstract

Access to healthy or diseased human neural tissue is a daunting task and represents a barrier for advancing our understanding about the cellular, genetic, and molecular mechanisms underlying neurogenesis and neurodegeneration. Reprogramming of somatic cells to pluripotency by transient expression of transcription factors was achieved a few years ago. Induced pluripotent stem cells (iPSC) from both healthy individuals and patients suffering from debilitating, life-threatening neurological diseases have been differentiated into several specific neuronal subtypes. An alternative emerging approach is the direct conversion of somatic cells (i.e., fibroblasts, blood cells, or glial cells) into neuron-like cells. However, to what extent neuronal direct conversion of diseased somatic cells can be achieved remains an open question. Optimization of current expansion and differentiation approaches is highly demanded to increase the differentiation efficiency of specific phenotypes of functional neurons from iPSCs or through somatic cell direct conversion. The realization of the full potential of iPSCs relies on the ability to precisely modify specific genome sequences. Genome editing technologies including zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeat/CAS9 RNA-guided nucleases have progressed very fast over the last years. The combination of genome-editing strategies and patient-specific iPSC biology will offer a unique platform for in vitro generation of diseased and corrected neural derivatives for personalized therapies, disease modeling and drug screening. Stem Cells 2014;32:2811–2817

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