Human iPSC lines are usually produced from fibroblasts isola

Human iPSC lines are usually produced from fibroblasts isolated from skin biopsies, a traumatic invasive procedure demanding local anesthesia and medical follow-up. Hair follicle (HF) plucking, however, is simple, painless and a non-invasive alternative procedure. In the genuine study demonstrating that skin fluoxetine hydrochloride can produce iPSC, HF has been suggested as an alternative source for cell reprogramming (Aasen et al., 2008) and our study confirms that as few as ten HF in anagen phase can be used to successfully reprogram keratinocytes into iPSC and shows that HF-iPSC can serve as an efficient model to obtain various types of donor-specific neuronal lineages. An additional advantage of HF, demonstrated in the present study, is the ability to store plucked HF in medium for at least 48h at room temperature, allowing exchange of materials between clinical centers and research laboratories. Taken together, these advantages suggest hair follicles as a material of choice for deriving of iPSC lines from a relatively large sample size of patients suffering from neuropsychiatric disorders. Moreover, the HF-keratinocytes, similar to neurons are derived from the same ectodermal embryonic layer, and thus, besides carrying an identical genetic load, could retain the same epigenetic alterations during early development. Indeed, it has been demonstrated that iPSC can retain epigenetic memory of the tissue of origin (Kim et al., 2010). It is therefore conceivable that iPSC derived from HF keratinocytes would retain conserved epigenetic insults that occurred during embryonic neuroectodermal fate in patients, which will enable studying epigenetic factors during normal and pathological neurodevelopment in vitro. One can argue that multifactorial pathologies are difficult to model with iPSC due to the heterogeneity of the genetic background and environmental factors involved in their etiology. Nevertheless, a recent study revealed abnormal neuronal connectivity in schizophrenic patient-derived iPSC, demonstrating the relevance of this approach (Brennand et al., 2011). In their study, commercially available skin-derived fibroblasts were used. However, the compliance of patients to skin biopsy is rather low and therefore hair follicles are an attractive and painless alternative to obtain large number of iPSC lines-and their derived neurons. Indeed, we have already produced iPSC lines from four schizophrenic patients with similar efficiency to that of healthy donors (data not shown). We believe that HF-iPSC-based models will facilitate the biological research of complex neurodevelopmental disorders and may provide new insights into neuron development in health and disease. In addition HF-iPSC may serve as a tool for the design of alternative therapeutics and for personalized pharmaco-genetic studies to optimize drug therapy for the benefit of the patients.
Materials and methods
Acknowledgments This work was supported by grants from the Agence Nationale de la Recherche (ANR-08-GENOPAT-024), L\'Oréal, the National Alliance for Research on Schizophrenia and Affective Disorders (NARSAD) and from the Chief Scientist, Ministry of Health, State of Israel. FJM was supported by an Else-Kröner Fresenius Stiftung fellowship. The authors thank G. Mostoslavsky (Boston University School of Medicine) for providing the STEMCCA vector and Bruno Bernard (L\'Oréal) for advices.