Generation of induced pluripotent stem cells (CSSi017-A)(12862) from an ALS patient carrying a repeat expansion in the C9orf72 gene

G Ruotolo; A D'Anzi; A Casamassa; M Mazzoni; D Ferrari; I Lombardi; R M Carletti; C D'Asdia; I Torrente; K Frezza; S Lattante; M Sabatelli; M Pennuto; A L Vescovi; J Rosati

doi:10.1016/j.scr.2024.103412

Generation of induced pluripotent stem cells (CSSi017-A)(12862) from an ALS patient carrying a repeat expansion in the C9orf72 gene

Stem Cell Res. 2024 Jun:77:103412. doi: 10.1016/j.scr.2024.103412. Epub 2024 Apr 10.

Authors

G Ruotolo¹, A D'Anzi², A Casamassa², M Mazzoni², D Ferrari³, I Lombardi³, R M Carletti³, C D'Asdia⁴, I Torrente⁴, K Frezza⁴, S Lattante⁵, M Sabatelli⁶, M Pennuto⁷, A L Vescovi¹, J Rosati⁸

Affiliations

¹ Cellular Reprogramming Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
² Cellular Reprogramming Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
³ Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
⁴ Medical Genetics Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
⁵ Medical Genetics Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Section of Genomic Medicine, Department of Health Sciences and Public Health, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, Rome, Italy; Experimental Medicine Department, Università del Salento, Lecce, Italy.
⁶ Neurology Unit, NeMO Clinical Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Section of Neurology, Department of Neurosciences, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, Rome, Italy.
⁷ Department of Biomedical Sciences, University of Padova, Padova, Italy; Veneto Institute of Molecular Medicine (VIMM), Padova, Italy.
⁸ Cellular Reprogramming Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. Electronic address: [email protected].

PMID: 38613988
DOI: 10.1016/j.scr.2024.103412

Abstract

Genetic expansions of the hexanucleotide repeats (GGGGCC) in the C9orf72 gene appear in approximately 40% of patients with familial ALS and 7% of patients with sporadic ALS in the European population, making this mutation one of the most prevalent genetic mutations in ALS. Here, we generated a human induced pluripotent stem cell (hiPSC) line from the dermal fibroblasts of a patient carrying a 56-repeat expansion in an ALS disease-causing allele of C9orf72. These iPSCs showed stable amplification in vitro with normal karyotype and high expression of pluripotent markers and differentiated spontaneously in vivo into three germ layers.

MeSH terms

Amyotrophic Lateral Sclerosis* / genetics
Amyotrophic Lateral Sclerosis* / pathology
C9orf72 Protein* / genetics
C9orf72 Protein* / metabolism
Cell Differentiation
Cell Line
DNA Repeat Expansion*
Fibroblasts / metabolism
Humans
Induced Pluripotent Stem Cells* / metabolism
Male

Substances

C9orf72 Protein
C9orf72 protein, human