Induced pluripotent stem cells from hair follicles to study neurodevelopmental disorders as ADHD

Prof. Dr. Edna Grünblatt
Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital
University of Zürich
edna.gruenblatt@kjpd.uzh.ch

ongoing

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental and psychiatric disorders in children and adolescents often to persist into adulthood. The causes and pathophysiology of ADHD are still unknown; nevertheless, evidences point to implication of genetic and environmental factors that probably affect brain maturation and development. To date, none of the existing models for ADHD (in vivo or in vitro) fully mimic the entire phenotypic spectrum or genetic background of the disorder, which is needed for elucidating the molecular pathomechanism or therapy response. Therefore, there is a great need to establish a model that mirrors the developmental alterations of ADHD. Reprogramming human somatic cells into induced pluripotent stem cells (hiPSC) and differentiating them into a neuronal lineage is a new, powerful technology that provides live human neurons for modelling complex genetic conditions, such as neurodevelopmental disorders (e.g., ADHD). The primary aim of the project is to establish a new, versatile, and de novo cell-based model for ADHD using hiPSC originating from the hair follicles (keratinocytes) of paediatric ADHD patients and controls. This unique cellular model will enable unprecedented investigation into the causative events of ADHD and the identification of specific biomarkers. Furthermore, this technology will allow therapeutics to be tested in cell types of interest, in a way that reflects response and effects reliably. Using this unique, patient-specific model we will try to find and characterize genetic alterations (mRNA, DNA polymorphism, epigenetic), possible altered neuronal pathways and changes in proteomics and broaden the understanding of ADHD’s causes.

Das Projekt in den Medien:

SRF PULS 02.05.2022  „Hyperaktivität-Erwachsene unter Dauerstrom“ von 12.47 min

Related publications

Lucia Dutan Polit, Ilse Eidhof, Rhiannon V. McNeill, Katherine M. Warre-Cornish, Cristine Marie Yde Ohki, Natalie Monet Walter, Carlo Sala, Chiara Verpelli, Franziska Radtke, Silvana Galderisi, Armida Mucci, Ginetta Collo, Frank Edenhofer, Maija L. Castrén, János M. Réthelyi, Morten Ejlersen, Sonja Simone Hohmann, Mirolyuba S. Ilieva, Renate Lukjanska, Rugile Matuleviciute, Tanja Maria Michel, Femke M.S. de Vrij, Steven A. Kushner, Bas Lendemeijer, Sarah Kittel-Schneider, Georg C. Ziegler, Doris Gruber-Schoffnegger, R. Jeroen Pasterkamp, Amal Kasri, Marie-Claude Potier, Jürgen A. Knoblich, Oliver Brüstle, Michael Peitz, Emilio Merlo Pich, Adrian J. Harwood, Elsa Abranches, Anna Falk, Anthony C. Vernon, Edna Grünblatt, Deepak P. Srivastava, Recommendations, guidelines, and best practice for the use of human induced pluripotent stem cells for neuropharmacological studies of neuropsychiatric disorders, Neuroscience Applied, 2023, 101125, ISSN 2772-4085, https://doi.org/10.1016/j.nsa.2023.101125.

Yde Ohki CM, Walter NM, Rickli M, Van Puyenbroeck P, Döring C, Hoffmann P, Herms S, Maria Werling A, Walitza S, Grünblatt E. Generation of induced pluripotent stem cells from two ADHD patients and two healthy controls. Stem Cell Res. 2023 Mar 27;69:103084. doi:10.1016/j.scr.2023.103084.

Yde Ohki CM, Walter NM, Bender A, Rickli M, Ruhstaller S, Walitza S, Grünblatt E. Growth rates of human induced pluripotent stem cells and neural stem cells from attention-deficit hyperactivity disorder patients: a preliminary study. J Neural Transm (Vienna). 2023 Mar;130(3):243-252. doi:10.1007/s00702-023-02600-1.

Yde Ohki CM, McNeill RV, Nieberler M, Radtke F, Kittel-Schneider S, Grünblatt E. Promising Developments in the Use of Induced Pluripotent Stem Cells in Research of ADHD. Curr Top Behav Neurosci. 2022;57:483-501. doi:10.1007/7854_2022_346.

Yde Ohki CM, Grossmann L, Döring C, Hoffmann P, Herms S, Werling AM, Walitza S, Grünblatt E. Generation of integration-free induced pluripotent stem cells from healthy individuals. Stem Cell Res. 2021 May;53:102269. doi:10.1016/j.scr.2021.102269.

Grossmann L, Yde Ohki CM, Döring C, Hoffmann P, Herms S, Werling AM, Walitza S, Grünblatt E. Generation of integration-free induced pluripotent stem cell lines from four pediatric ADHD patients. Stem Cell Res. 2021 May;53:102268. doi:10.1016/j.scr.2021.102268.

Filice F, Schwaller B, Michel TM, Grünblatt E. Profiling parvalbumin interneurons using iPSC: challenges and perspectives for Autism Spectrum Disorder (ASD). Mol Autism. 2020 Jan 29;11(1):10. doi:10.1186/s13229-020-0314-0.

Re S, Dogan AA, Ben-Shachar D, Berger G, Werling AM, Walitza S, Grünblatt E. Improved Generation of Induced Pluripotent Stem Cells From Hair Derived Keratinocytes - A Tool to Study Neurodevelopmental Disorders as ADHD. Front Cell Neurosci. 2018 Sep 25;12:321. doi:10.3389/fncel.2018.00321.