TY - JOUR
T1 - A transcriptomic signature of X chromosome overdosage in Saudi Klinefelter syndrome induced pluripotent stem cells
AU - Astro, Veronica
AU - Fiacco, Elisabetta
AU - Cardona-Londoño, Kelly Johanna
AU - De Toma, Ilario
AU - Alzahrani, Hams Saeed
AU - Alama, Jumana
AU - Kokandi, Amal
AU - Abdel-Meguid Hamoda, Taha Abo Almagd
AU - Felemban, Majed
AU - Adamo, Antonio
N1 - Funding Information:
This work was supported by KAUST Smart Health Initiative grant REI/1/4471-01-01 to A A and baseline funding (BAS 1077-01-01) to A A.
Publisher Copyright:
© 2023 the author(s) Published by Bioscientifica Ltd.
PY - 2023/5
Y1 - 2023/5
N2 - 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 ethnicities. 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 controls. 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.
AB - 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 ethnicities. 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 controls. 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.
KW - escape genes
KW - induced pluripotent stem cells
KW - Klinefelter syndrome
KW - pseudoautosomal region
KW - X chromosome
UR - http://www.scopus.com/inward/record.url?scp=85159414473&partnerID=8YFLogxK
U2 - 10.1530/EC-22-0515
DO - 10.1530/EC-22-0515
M3 - Article
C2 - 36971776
AN - SCOPUS:85159414473
SN - 2049-3614
VL - 12
JO - Endocrine Connections
JF - Endocrine Connections
IS - 5
M1 - e220515
ER -
