title: Derivation of Huntington's disease-affected human embryonic stem cell lines.
abstract: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by an expansion of cytosine-adenine-guanine (CAG) repeats in the Huntingtin gene Htt. To facilitate research into HD, we have derived 4 human embryonic stem cell (hESC) lines containing ≥ 40 CAG repeats in exon 1 of Htt: SIVF017-HD (CAG₄₀), SIVF018-HD (CAG₄₆), SIVF020-HD (CAG₄₈), and SIVF046-HD (CAG₄₅). Additionally, we have derived a normal sibling-matched control for SIVF020-HD, cell line SIVF019. All 5 hESC lines had a normal karyotype, expressed pluripotency markers including Oct4, SSEA3, and Tra-1-81, and could be maintained in culture for multiple (>40) passages. Teratoma studies revealed that the hESC lines were capable of differentiating into cells representative of the 3 germ layers. Furthermore, in vitro neuronal differentiation experiments have confirmed that the hESC lines were able to generate MAP2-positive neuronal cells that express the Htt protein. Combined, these experiments confirm that the cell lines represent pluripotent stem cell lines. These HD-affected hESC lines will be made available to biomedical research laboratories and will provide a valuable tool to investigate the mechanisms and potential treatments for HD.
authors.affiliation: Sydney IVF Stem Cells, Sydney, Australia.
authors.forename: Cara K
authors.initials: CK
authors.lastname: Bradley
authors.forename: Heather A
authors.initials: HA
authors.lastname: Scott
authors.forename: Omar
authors.initials: O
authors.lastname: Chami
authors.forename: Teija T
authors.initials: TT
authors.lastname: Peura
authors.forename: Biljana
authors.initials: B
authors.lastname: Dumevska
authors.forename: Uli
authors.initials: U
authors.lastname: Schmidt
authors.forename: Tomas
authors.initials: T
authors.lastname: Stojanov
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D002454:Cell Differentiation; D048430:Cell Shape; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000637:transplantation; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology*; D007621:Karyotyping; D051379:Mice; D016513:Mice, SCID; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016254:Mutagenesis, Insertional; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D011110:Polymorphism, Genetic; D011509:Proteoglycans / Q000378:metabolism; D055746:Stage-Specific Embryonic Antigens / Q000378:metabolism; D013724:Teratoma / Q000473:pathology; D019680:Trinucleotide Repeat Expansion
chemical_list: D000954:Antigens, Surface; C086055:HTT protein, human; D000071058:Huntingtin Protein; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D011509:Proteoglycans; D055746:Stage-Specific Embryonic Antigens; C107064:TRA-1-60 antigen, human; C519803:TRA-1-81 antigen, human; C066584:stage-specific embryonic antigen-4