Generation of three spinocerebellar ataxia type-12 patients derived induced pluripotent stem cell lines (IGIBi002-A, IGIBi003-A and IGIBi004-A)

Abstract

Spinocerebellar ataxia type-12 (SCA12) is a neurological disorder caused due to triplet (CAG) repeat expansion in 5' UTR of PPP2R2B. It is one of the most prominent SCA-subtype in Indian population and till date no patient specific models have been described. Human-induced-pluripotent-stem cell (HiPSC) based disease modelling has become the next generation tool for studying various human pathologies. In the present study we established three SCA12 patient specific iPSC lines. All the generated lines have shown pluripotency markers, normal karyotype, in-vitro three germ layers differentiation potential, vector clearance, SCA12 mutation, parental genomic identity and contamination free culture.

Molecular clues unveiling spinocerebellar ataxia type-12 pathogenesis

“…SK-NSH cell lines: RNA foci; HEK293: Demonstration of RAN; NSCs (iPSC derived): 2 NSCs from control subjects (10223, D161), 3 SCA12 patients [21/14 (IGIBi004-A), 2555 (IGIBi002-A), 11/08 (IGIBi003-A)]; iPSC: reprogrammed LCLs; 44 Differentiated neurons (10223-control and 2555-case [IGIBi002-A]). Refer Table 1 .…”

“…Neural stem cells (NSCs) were differentiated from three Spinocerebellar ataxia type-12 iPSCs (IGIBi002-A, IGIBi003-A, and IGIBi004-A) (published previously), 44 and two Control iPSCs, ADBSi001-A, 38 and one in house iPSC generated from a healthy individual (Cell line ID. 10223) ( Figures S5 and S6 ) by using previously published protocol 39 with slight modifications.…”

In vitro Models of Neurodegenerative Diseases

“…PD affects 1-2% Lotharius et al, 2005;Van Vliet et al, 2008;Zhang et al, 2014;Smirnova et al, 2016;Harischandra et al, 2019;Taylor-Whiteley et al, 2019Tan et al, 2018 Amyotrophic lateral sclerosis Pansarasa et al, 2018Chen et al, 2014Fujimori et al, 2018Dimos et al, 2008Burkhardt et al, 2013;Sareen et al, 2013Smith et al, 2015Krencik et al, 2017;Osaki et al, 2018. Huntington's disease Bidollari et al, 2018Szlachcic et al, 2017An et al, 2012Camnasio et al, 2012;Juopperi et al, 2012;Nekrasov et al, 2016;Vigont et al, 2018;Mehta et al, 2018Virlogeux et al, 2018 Spinal muscular atrophy Not available Not available Ebert et al, 2009;Fuller et al, 2015;Zhang et al, 2017a;Valetdinova et al, 2019. Hor et al, 2018 Spinocerebellar ataxia Kumar D. et al, 2018;Maguire et al, 2019Wang et al, 2015Xia et al, 2013Marthaler et al, 2016;Nayler et al, 2017;Sun et al, 2018;Chuang et al, 2019;Yang et al, 2019.…”

Human Induced Pluripotent Stem Cell-Based Modelling of Spinocerebellar Ataxias

“…A single hiPSC model will not be able to recapitulate the different aspects of pathophysiology in all SCA patients. Nowadays, many new hiPSC lines carrying different genetic variants of SCAs have been generated and registered [136][137][138][139][140][141][142][143][144][145][146][147][148][149], which makes it easier to utilize multiple clones from multiple patients. Among these lines, also isogenic control lines created by CRISPR/Cas are listed [150][151][152], which can serve as proper controls that take genetic background into account as an important variable.…”