A13 Proteomic characterization of human induced pluripotent and neural stem cell lines from hd patients and healthy controls

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 93; no. Suppl 1; p. A5
• Main Authors: Vodickova Kepkova, Katerina, Tyleckova, Jirina, Cervenka, Jakub, Budkova, Katerina, Poliakh, Ievgeniia, Vodicka, Petr
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.09.2022; BMJ Publishing Group LTD
• Subjects: A: Pathogenic mechanisms; Cell adhesion & migration; Huntingtons disease; Huntington’s disease; iPSC; LC-MS; NSC; Proteins; Proteomics; Stem cells
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp-2022-ehdn.13

BackgroundHuntington disease (HD) is an incurable monogenic autosomal dominant neurodegeneration. The expansion of CAG tract in HTT gene over 35 repeats encodes extended stretch of glutamines, which confers toxic gain of function to the mutated huntingtin protein (mHTT), leading to neuronal death. Normal HTT is also important for neural system development, but to what extent is the loss of normal protein function part of HD phenotype is unclear. Human neural stem cells (NSCs) represent useful in vitro system to study cell autonomous and non-autonomous roles of HTT protein.MethodsWe prepared neural stem cells (NSCs) derived from 3 control and 3 HD human induced pluripotent stem cells (iPSCs). We performed whole proteome profiling using LC-MS proteomics and additionally analysed expression of cell surface N-glycoproteins using cell surface glycocapturing.ResultsWe quantified over 3000 proteins using LC-MS proteomics. At the iPSC stage, only 24 proteins were differentially expressed between HD and control lines, while at the NSC stage, over 100 proteins were significantly changed. Four cell surface expressed proteins were significantly changed between HD and control NSCs, PDLIM5 (PDZ And LIM Domain 5) and HSPA13 (Heat Shock Protein Family A Hsp70 Member 13) were more abundant in HD lines, while L1CAM (Neural Cell Adhesion Molecule L1) and CXADR (Coxsackie Virus And Adenovirus Receptor, CXADR Ig-Like Cell Adhesion Molecule) were more abundant in control lines.ConclusionWe identified changes in protein expression between HD and control NSCs. Biological relevance of identified changes is currently under study.