Derivation and investigation of the first human cell-based model of Beckwith-Wiedemann syndrome
Genomic imprinting is a rare form of gene expression in mammals in which a small number of genes are expressed in a parent-of-origin-specific manner. The aetiology of human imprinting disorders is diverse and includes chromosomal abnormalities, mutations, and epigenetic dysregulation of imprinted ge...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-12-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2020.1861172 |
| _version_ | 1797678794817929216 |
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| author | Suhee Chang Stella K. Hur Natali S. Sobel Naveh Joanne L. Thorvaldsen Deborah L. French Alyssa L Gagne Chintan D. Jobaliya Montserrat C. Anguera Marisa S. Bartolomei Jennifer M Kalish |
| author_facet | Suhee Chang Stella K. Hur Natali S. Sobel Naveh Joanne L. Thorvaldsen Deborah L. French Alyssa L Gagne Chintan D. Jobaliya Montserrat C. Anguera Marisa S. Bartolomei Jennifer M Kalish |
| author_sort | Suhee Chang |
| collection | DOAJ |
| description | Genomic imprinting is a rare form of gene expression in mammals in which a small number of genes are expressed in a parent-of-origin-specific manner. The aetiology of human imprinting disorders is diverse and includes chromosomal abnormalities, mutations, and epigenetic dysregulation of imprinted genes. The most common human imprinting disorder is Beckwith-Wiedemann syndrome (BWS), frequently caused by uniparental isodisomy and DNA methylation alterations. Because these lesions cannot be easily engineered, induced pluripotent stem cells (iPSC) are a compelling alternative. Here, we describe the first iPSC model derived from patients with BWS. Due to the mosaic nature of BWS patients, both BWS and non-BWS iPSC lines were derived from the same patient’s fibroblasts. Importantly, we determine that DNA methylation and gene expression patterns of the imprinted region in the iPSC lines reflect the parental cells and are stable over time. Additionally, we demonstrate that differential expression in insulin signalling, cell proliferation, and cell cycle pathways was seen in hepatocyte lineages derived from BWS lines compared to controls. Thus, this cell based-model can be used to investigate the role of imprinting in the pathogenesis of BWS in disease-relevant cell types. |
| first_indexed | 2024-03-11T23:05:07Z |
| format | Article |
| id | doaj.art-03d418f378ec4d8dbddcd0b45ec27f03 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:05:07Z |
| publishDate | 2021-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-03d418f378ec4d8dbddcd0b45ec27f032023-09-21T13:09:25ZengTaylor & Francis GroupEpigenetics1559-22941559-23082021-12-0116121295130510.1080/15592294.2020.18611721861172Derivation and investigation of the first human cell-based model of Beckwith-Wiedemann syndromeSuhee Chang0Stella K. Hur1Natali S. Sobel Naveh2Joanne L. Thorvaldsen3Deborah L. French4Alyssa L Gagne5Chintan D. Jobaliya6Montserrat C. Anguera7Marisa S. Bartolomei8Jennifer M Kalish9Perelman School of Medicine, University of PennsylvaniaPerelman School of Medicine, University of PennsylvaniaChildren’s Hospital of PhiladelphiaPerelman School of Medicine, University of PennsylvaniaChildren’s Hospital of PhiladelphiaChildren’s Hospital of PhiladelphiaChildren’s Hospital of PhiladelphiaUniversity of Pennsylvania School of Veterinary MedicinePerelman School of Medicine, University of PennsylvaniaChildren’s Hospital of PhiladelphiaGenomic imprinting is a rare form of gene expression in mammals in which a small number of genes are expressed in a parent-of-origin-specific manner. The aetiology of human imprinting disorders is diverse and includes chromosomal abnormalities, mutations, and epigenetic dysregulation of imprinted genes. The most common human imprinting disorder is Beckwith-Wiedemann syndrome (BWS), frequently caused by uniparental isodisomy and DNA methylation alterations. Because these lesions cannot be easily engineered, induced pluripotent stem cells (iPSC) are a compelling alternative. Here, we describe the first iPSC model derived from patients with BWS. Due to the mosaic nature of BWS patients, both BWS and non-BWS iPSC lines were derived from the same patient’s fibroblasts. Importantly, we determine that DNA methylation and gene expression patterns of the imprinted region in the iPSC lines reflect the parental cells and are stable over time. Additionally, we demonstrate that differential expression in insulin signalling, cell proliferation, and cell cycle pathways was seen in hepatocyte lineages derived from BWS lines compared to controls. Thus, this cell based-model can be used to investigate the role of imprinting in the pathogenesis of BWS in disease-relevant cell types.http://dx.doi.org/10.1080/15592294.2020.1861172beckwith-wiedemann syndromeinduced pluripotent stem cellsimprinting |
| spellingShingle | Suhee Chang Stella K. Hur Natali S. Sobel Naveh Joanne L. Thorvaldsen Deborah L. French Alyssa L Gagne Chintan D. Jobaliya Montserrat C. Anguera Marisa S. Bartolomei Jennifer M Kalish Derivation and investigation of the first human cell-based model of Beckwith-Wiedemann syndrome Epigenetics beckwith-wiedemann syndrome induced pluripotent stem cells imprinting |
| title | Derivation and investigation of the first human cell-based model of Beckwith-Wiedemann syndrome |
| title_full | Derivation and investigation of the first human cell-based model of Beckwith-Wiedemann syndrome |
| title_fullStr | Derivation and investigation of the first human cell-based model of Beckwith-Wiedemann syndrome |
| title_full_unstemmed | Derivation and investigation of the first human cell-based model of Beckwith-Wiedemann syndrome |
| title_short | Derivation and investigation of the first human cell-based model of Beckwith-Wiedemann syndrome |
| title_sort | derivation and investigation of the first human cell based model of beckwith wiedemann syndrome |
| topic | beckwith-wiedemann syndrome induced pluripotent stem cells imprinting |
| url | http://dx.doi.org/10.1080/15592294.2020.1861172 |
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