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Front. Cell. Neurosci. | doi: 10.3389/fncel.2018.00321

Improved generation of induced pluripotent stem cells from hair derived keratinocytes - a tool to study neurodevelopmental disorders as ADHD

  • 1Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, Universität Zürich, Switzerland
  • 2Department of Psychiatry, Rambam Health Care Campus and B. Rappaport Faculty of Medicine, Rappaport Family Institute for Research in Medical Sciences, Technion – Israel Institute of Technology, Israel
  • 3Zentrum für Neurowissenschaften Zürich, Universität Zürich, Switzerland

In the last decade, there is an increasing application of induced pluripotent stem cells (iPSCs) for disease modelling. The iPSC technology enables the study of patient-specific neuronal cell lines in vitro to evaluate dysfunction at the cellular level and identify the responsible genetic factors. This approach might be particularly valuable for filling the gap of knowledge at the cellular and molecular levels underlying the pathophysiology of various neurodevelopmental and/or psychiatric disorders, such as attention-deficit hyperactivity disorder (ADHD). However, the invasiveness of skin biopsy or blood withdrawal might represent a major impediment in such protected population. Using hair derived keratinocytes as starting somatic cells circumvents this problem as sample collections can be performed noninvasively.
Here we describe an improved, convenient, standardized and effective method to culture and reprogram hair derived keratinocytes from three healthy controls and one ADHD patient into iPSCs, which in turn will be used to generate differentiated neuronal cells. All the cell types were maintained in highly defined, serum-free conditions and showed expression of the respective key marker genes, assessed by both immunocytochemistry and qRT-PCR. The described in vitro personalized neuronal model has its advantage in modelling neurodevelopmental trajectories since it can recapitulate key processes of brain development at the cellular and molecular level and is intended to be used as for example studying ADHD etiopathology.

Keywords: iPSCs, keratinocyte, Hair Follicle, hair follicle stem cell, reprogramming, ADHD, neurodevelopment, disease modelling, Stem Cells

Received: 23 May 2018; Accepted: 04 Sep 2018.

Edited by:

Dirk Schubert, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Netherlands

Reviewed by:

Julien Rossignol, Central Michigan University, United States
Jerome Mertens, Salk Institute for Biological Studies, United States  

Copyright: © 2018 Re, Dogan, Ben-Shachar, Berger, Werling, Walitza and Grünblatt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Edna Grünblatt, GRÜNBLATT., Universität Zürich, Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, Zürich, 8952, Schweiz, Switzerland,