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Reprogramming fibroblasts and peripheral blood cells from a C9ORF72 patient: A proof-of-principle study |
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| Authors: | Donatella Bardelli Francesca Sassone Claudia Colombrita Clara Volpe Valentina Gumina Silvia Peverelli Ilaria Catusi Antonia Ratti Vincenzo Silani Patrizia Bossolasco |
| Institution: | 1. Department of Neurology and Laboratory of Neuroscience, Istituto Auxologico Italiano IRCCS, Milan, Italy
“Aldo Ravelli” Center for Neurotechnology and Experimental Brain Therapeutics, Università degli Studi di Milano, Milan, Italy;2. Department of Neurology and Laboratory of Neuroscience, Istituto Auxologico Italiano IRCCS, Milan, Italy;3. Department of Neurology and Laboratory of Neuroscience, Istituto Auxologico Italiano IRCCS, Milan, Italy Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy;4. Lab. di Citogenetica Medica, IRCCS Istituto Auxologico Italiano, Milano, Italy;5. Department of Neurology and Laboratory of Neuroscience, Istituto Auxologico Italiano IRCCS, Milan, Italy “Aldo Ravelli” Center for Neurotechnology and Experimental Brain Therapeutics, Università degli Studi di Milano, Milan, Italy Dino Ferrari” Center, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy |
| Abstract: | As for the majority of neurodegenerative diseases, pathological mechanisms of amyotrophic lateral sclerosis (ALS) have been challenging to study due to the difficult access to alive patients' cells. Induced pluripotent stem cells (iPSCs) offer a useful in vitro system for modelling human diseases. iPSCs can be theoretically obtained by reprogramming any somatic tissue although fibroblasts (FB) remain the most used cells. However, reprogramming peripheral blood cells (PB) may offer significant advantages. In order to investigate whether the choice of starting cells may affect reprogramming and motor neuron (MNs) differentiation potential, we used both FB and PB from a same C9ORF72-mutated ALS patient to obtain iPSCs and compared several hallmarks of the pathology. We found that both iPSCs and MNs derived from the two tissues showed identical properties and features and can therefore be used interchangeably, giving the opportunity to easily obtain iPSCs from a more manageable source of cells, such as PB. |
| Keywords: | amyotrophic lateral sclerosis C9ORF72 fibroblasts iPSCs motor neuron peripheral blood cells repeat expansion reprogramming RNA foci TDP-43 |