A transcriptomic signature of X chromosome overdosage in Saudi Klinefelter syndrome induced pluripotent stem cells
Objective: The transcriptional landscape of Klinefelter syndrome (KS) during early embryogenesis remains elusive. This study aimed to evaluate the impact of X chromosome overdosage in 47,XXY males induced pluripotent stem cells (iPSCs) obtained from patients with different genomic backgrounds and et...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Bioscientifica
2023-05-01
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| Series: | Endocrine Connections |
| Subjects: | |
| Online Access: | https://ec.bioscientifica.com/view/journals/ec/12/5/EC-22-0515.xml |
| _version_ | 1827955924560510976 |
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| author | Veronica Astro Elisabetta Fiacco Kelly Johanna Cardona-Londoño Ilario De Toma Hams Saeed Alzahrani Jumana Alama Amal Kokandi Taha Abo-Almagd Abdel-Meguid Hamoda Majed Felemban Antonio Adamo |
| author_facet | Veronica Astro Elisabetta Fiacco Kelly Johanna Cardona-Londoño Ilario De Toma Hams Saeed Alzahrani Jumana Alama Amal Kokandi Taha Abo-Almagd Abdel-Meguid Hamoda Majed Felemban Antonio Adamo |
| author_sort | Veronica Astro |
| collection | DOAJ |
| description | Objective: The transcriptional landscape of Klinefelter syndrome (KS) during early embryogenesis remains elusive. This study aimed to evaluate the impact of X chromosome overdosage in 47,XXY males induced pluripotent stem cells (iPSCs) obtained from patients with different genomic backgrounds and et hnicities.
Design and method: We derived and characterized 15 iPSC lines from four Saudi 47,XXY KS patients and one Saudi 46,XY male. We performed a comparative transcriptional analysis using the Saudi KS-iPSCs and a cohort of European and North American KS-iPSCs.
Results: We identified a panel of X-linked and autosomal genes commonly dysregulated in Saudi and European/North American KS-iPSCs vs 46,XY control s. Our findings demonstrate that seven PAR1 and nine non-PAR escape genes are consistently dysregulated and mostly display comparable transcriptional levels in both groups. Finally, we focused on genes commonly dysregulated in both iPSC cohorts and identified several gene-ontology categories highly relevant to KS physiopathology, including aberrant cardiac muscle contractility, skeletal muscle defects, abnormal synaptic transmission, and behavioral alterations.
Conclusions: Our results indicate that a transcriptomic signature of X chromosome overdosage in KS is potentially attributable to a subset of X-linked genes sensitive to sex chromosome dosage and escaping X inactivation, regardless of the geographical area of origin, ethnicity, and genetic makeup. |
| first_indexed | 2024-04-09T14:55:52Z |
| format | Article |
| id | doaj.art-e458266cbab54a838ebbd856aaec132c |
| institution | Directory Open Access Journal |
| issn | 2049-3614 |
| language | English |
| last_indexed | 2024-04-09T14:55:52Z |
| publishDate | 2023-05-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Connections |
| spelling | doaj.art-e458266cbab54a838ebbd856aaec132c2023-05-02T07:07:48ZengBioscientificaEndocrine Connections2049-36142023-05-01125112https://doi.org/10.1530/EC-22-0515A transcriptomic signature of X chromosome overdosage in Saudi Klinefelter syndrome induced pluripotent stem cellsVeronica Astro0Elisabetta Fiacco1Kelly Johanna Cardona-Londoño2Ilario De Toma3Hams Saeed Alzahrani4Jumana Alama5Amal Kokandi6Taha Abo-Almagd Abdel-Meguid Hamoda7Majed Felemban8Antonio Adamo9Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi ArabiaBiological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi ArabiaBiological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi ArabiaSequentia Biotech SL, Barcelona, SpainDepartment of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Dermatology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Urology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia; Center of Innovation in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi ArabiaObjective: The transcriptional landscape of Klinefelter syndrome (KS) during early embryogenesis remains elusive. This study aimed to evaluate the impact of X chromosome overdosage in 47,XXY males induced pluripotent stem cells (iPSCs) obtained from patients with different genomic backgrounds and et hnicities. Design and method: We derived and characterized 15 iPSC lines from four Saudi 47,XXY KS patients and one Saudi 46,XY male. We performed a comparative transcriptional analysis using the Saudi KS-iPSCs and a cohort of European and North American KS-iPSCs. Results: We identified a panel of X-linked and autosomal genes commonly dysregulated in Saudi and European/North American KS-iPSCs vs 46,XY control s. Our findings demonstrate that seven PAR1 and nine non-PAR escape genes are consistently dysregulated and mostly display comparable transcriptional levels in both groups. Finally, we focused on genes commonly dysregulated in both iPSC cohorts and identified several gene-ontology categories highly relevant to KS physiopathology, including aberrant cardiac muscle contractility, skeletal muscle defects, abnormal synaptic transmission, and behavioral alterations. Conclusions: Our results indicate that a transcriptomic signature of X chromosome overdosage in KS is potentially attributable to a subset of X-linked genes sensitive to sex chromosome dosage and escaping X inactivation, regardless of the geographical area of origin, ethnicity, and genetic makeup.https://ec.bioscientifica.com/view/journals/ec/12/5/EC-22-0515.xmlklinefelter syndromex chromosomepseudoautosomal regionescape genesinduced pluripotent stem cells |
| spellingShingle | Veronica Astro Elisabetta Fiacco Kelly Johanna Cardona-Londoño Ilario De Toma Hams Saeed Alzahrani Jumana Alama Amal Kokandi Taha Abo-Almagd Abdel-Meguid Hamoda Majed Felemban Antonio Adamo A transcriptomic signature of X chromosome overdosage in Saudi Klinefelter syndrome induced pluripotent stem cells Endocrine Connections klinefelter syndrome x chromosome pseudoautosomal region escape genes induced pluripotent stem cells |
| title | A transcriptomic signature of X chromosome overdosage in Saudi Klinefelter syndrome induced pluripotent stem cells |
| title_full | A transcriptomic signature of X chromosome overdosage in Saudi Klinefelter syndrome induced pluripotent stem cells |
| title_fullStr | A transcriptomic signature of X chromosome overdosage in Saudi Klinefelter syndrome induced pluripotent stem cells |
| title_full_unstemmed | A transcriptomic signature of X chromosome overdosage in Saudi Klinefelter syndrome induced pluripotent stem cells |
| title_short | A transcriptomic signature of X chromosome overdosage in Saudi Klinefelter syndrome induced pluripotent stem cells |
| title_sort | transcriptomic signature of x chromosome overdosage in saudi klinefelter syndrome induced pluripotent stem cells |
| topic | klinefelter syndrome x chromosome pseudoautosomal region escape genes induced pluripotent stem cells |
| url | https://ec.bioscientifica.com/view/journals/ec/12/5/EC-22-0515.xml |
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