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1.
Stem Cell Res ; 71: 103143, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37343429

RESUMO

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder caused by loss of paternal expression of imprinted genes on chromosome 15q11-q13. We established a human induced pluripotent stem cell line (hiPSC), ZIPi021-A, from fibroblasts of a 4-year-old female PWS patient with the subtype of maternal uniparental disomy (mUPD). The generated hiPSC line was transgene-free, expressed pluripotency markers and showed the ability to differentiate into all three germ layers in vitro. The ZIPi021-A hiPSC line could be used as a cellular model for PWS in humans.


Assuntos
Células-Tronco Pluripotentes Induzidas , Transtornos do Neurodesenvolvimento , Síndrome de Prader-Willi , Feminino , Humanos , Pré-Escolar , Síndrome de Prader-Willi/genética , Dissomia Uniparental/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Fibroblastos/metabolismo , Cromossomos Humanos Par 15/genética
2.
Stem Cell Reports ; 16(10): 2488-2502, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34560000

RESUMO

Therapeutic application of induced pluripotent stem cell (iPSC) derivatives requires comprehensive assessment of the integrity of their nuclear and mitochondrial DNA (mtDNA) to exclude oncogenic potential and functional deficits. It is unknown, to which extent mtDNA variants originate from their parental cells or from de novo mutagenesis, and whether dynamics in heteroplasmy levels are caused by inter- and intracellular selection or genetic drift. Sequencing of mtDNA of 26 iPSC clones did not reveal evidence for de novo mutagenesis, or for any selection processes during reprogramming or differentiation. Culture expansion, however, selected against putatively actionable mtDNA mutations. Altogether, our findings point toward a scenario in which intracellular selection of mtDNA variants during culture expansion shapes the mutational landscape of the mitochondrial genome. Our results suggest that intercellular selection and genetic drift exert minor impact and that the bottleneck effect in context of the mtDNA genetic pool might have been overestimated.


Assuntos
Diferenciação Celular , Reprogramação Celular , DNA Mitocondrial/genética , Células-Tronco Pluripotentes Induzidas/fisiologia , Mitocôndrias/genética , Mutação , Seleção Genética , Técnicas de Cultura de Células , Genoma Mitocondrial , Instabilidade Genômica , Humanos
3.
Stem Cell Res ; 52: 102206, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33571874

RESUMO

Transgenic hiPSC lines carrying reporter genes represent valuable tools for functional characterization of iPSC derivatives, disease modelling and clinical evaluation of cell therapies. Here, the hiPSC line 'Phoenix' (Haase et al., 2017) was genetically engineered using TALEN-based integration of the calcium sensor GCaMP6f and RedStarnuc reporter into the AAVS1 site. Characterization of undifferentiated cells and functional investigation of hiPSC-derived cardiomyocytes-containing BCTs showed a strong intracellular calcium transient-dependent GCaMP6f and eminent RedStarnuc signal. Therefore, our dual reporter line provides an excellent tool to facilitate monitoring of engraftment, calcium fluctuations and coupling of iPSC derivatives such as cardiomyocytes in vitro and in vivo in animal models.


Assuntos
Células-Tronco Pluripotentes Induzidas , Animais , Cálcio , Diferenciação Celular , Genes Reporter , Engenharia Genética , Humanos , Miócitos Cardíacos
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