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DNA microarrays of Turner Syndrome induced pluripotent stem cells


ABSTRACT: We have generated iPSCs from monosomy X (Turner Syndrome), trisomy 8 (Warkany Syndrome 2), trisomy 13 (Patau Syndrome) and partial trisomy 11;22 (Emanuel Syndrome), using either skin fibroblasts from affected individuals or amniocytes from antenatal diagnostic tests. These cell lines stably maintain the karyotype of the donors and behave like embryonic stem cells (ESCs) in all tested assays. Turner Syndrome iPSCs were used for further studies including global gene expression analysis and tissue-specific directed differentiation. Multiple clones displayed lower levels of the pseudoautosomal genes ASMTL and PPP2R3B than the controls. Moreover, they could be transformed into neural-like, hepatocyte-like and heart-like cells but displayed insufficient up-regulation of the pseudoautosomal placental gene CSF2RA during embryoid body (EB) formation. These data support that abnormal organogenesis and early lethality in Turner Syndrome are not caused by a tissue-specific differentiation blockade but rather involves other abnormalities including impaired placentation. Global gene expression profiling with DNA microarrays showed that 3 TS iPSC clones corresponding to the same patient showed a global gene expression pattern similar to ESCs and euploid iPSCs, and very different from donor cells .We detected transcriptomic changes between TS iPSCs and the other ESCs/iPSCs but these variations did not follow a pattern and in fact all pluripotent cell lines clustered together. For DNA microarray analysis, all cells were treated with Trizol, followed by RNA extraction and hybridization.

ORGANISM(S): Homo sapiens

SUBMITTER: wang xianming 

PROVIDER: E-GEOD-32527 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Many human diseases share a developmental origin that manifests during childhood or maturity. Aneuploid syndromes are caused by supernumerary or reduced number of chromosomes and represent an extreme example of developmental disease, as they have devastating consequences before and after birth. Investigating how alterations in gene dosage drive these conditions is relevant because it might help treat some clinical aspects. It may also provide explanations as to how quantitative differences in ge  ...[more]

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