biostudies-literatureDafinca RMedical Research CouncilMotor Neurone Disease AssociationWellcome TrustParkinson's UK2063-78https://www.ebi.ac.uk/biostudies/studies/S-EPMC4979662biostudies-literatureUnknown34(8)An expanded hexanucleotide repeat in a noncoding region of the C9orf72 gene is a major cause of amyotrophic lateral sclerosis (ALS), accounting for up to 40% of familial cases and 7% of sporadic ALS in European populations. We have generated induced pluripotent stem cells (iPSCs) from fibroblasts of patients carrying C9orf72 hexanucleotide expansions, differentiated these to functional motor and cortical neurons, and performed an extensive phenotypic characterization. In C9orf72 iPSC-derived motor neurons, decreased cell survival is correlated with dysfunction in Ca(2+) homeostasis, reduced levels of the antiapoptotic protein Bcl-2, increased endoplasmic reticulum (ER) stress, and reduced mitochondrial membrane potential. Furthermore, C9orf72 motor neurons, and also cortical neurons, show Stem cells (Dayton, Ohio)C9orf72 Hexanucleotide Expansions Are Associated with Altered Endoplasmic Reticulum Calcium Homeostasis and Stress Granule Formation in Induced Pluripotent Stem Cell-Derived Neurons from Patients with Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.PMC4979662MR/M024962/1MR/P007023/1MC_EX_MR/N50192X/1TALBOT/OCT15/886-792MR/L023784/2MR/L023784/1TURNER/JAN13/944-795WADE-MARTINS/OCT13/867-792TALBOT-MUTIHAC/APR15/832-791MR/L002167/1090532/Z/09/ZSCABER/JULY13/945-795TALBOT/JULY13/820-791J-1403MR/K01014X/1Wade-Martins RLalic TTurner MRWeir GVowles JBrowne CScaber JTalbot KNakanishi MAbabneh NDouglas AGChristian HFletcher-Jones ADafinca RCowley SAfalseC9orf72 Hexanucleotide Expansions Are Associated with Altered Endoplasmic Reticulum Calcium Homeostasis and Stress Granule Formation in Induced Pluripotent Stem Cell-Derived Neurons from Patients with Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.An expanded hexanucleotide repeat in a noncoding region of the C9orf72 gene is a major cause of amyotrophic lateral sclerosis (ALS), accounting for up to 40% of familial cases and 7% of sporadic ALS in European populations. We have generated induced pluripotent stem cells (iPSCs) from fibroblasts of patients carrying C9orf72 hexanucleotide expansions, differentiated these to functional motor and cortical neurons, and performed an extensive phenotypic characterization. In C9orf72 iPSC-derived motor neurons, decreased cell survival is correlated with dysfunction in Ca(2+) homeostasis, reduced levels of the antiapoptotic protein Bcl-2, increased endoplasmic reticulum (ER) stress, and reduced mitochondrial membrane potential. Furthermore, C9orf72 motor neurons, and also cortical neurons, show 2016-01-01T00:00:00Z2016 Aug2026-04-30T03:40:04.716Z2019-03-27T02:20:19ZS-EPMC49796622709728310.1002/stem.2388