Aberrant Regulation of endMT in Turner Syndrome: Implications for the Pathogenesis of Congenital Cardiovascular Disease Article Swipe
Eric Ivan Garcia Huitron
,
Xiaoying Zhang
,
Lance Babcock
,
K. Jane Grande‐Allen
,
Siddharth K. Prakash
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.21542/gcsp.2025.hvbte.42
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.21542/gcsp.2025.hvbte.42
Turner syndrome (TS) is caused by the partial/complete absence of one sex chromosome and affects 1 in 2500 liveborn infants. Bicuspid aortic valve, and thoracic aortic aneurysms are more prevalent in TS compared to the general population. We hypothesize that cardiovascular abnormalities caused by endothelial-mesenchymal transition (endMT) in the embryo and adulthood are in part aberrant responses to shear stress. The objective of this study was to define functional and transcriptomic differences between euploid (46,XX) and aneuploid (45,X) induced pluripotent stem cell (iPSC)-derived endothelial cells (ECs) from adult donors with mosaic TS. iPSCs were reprogrammed from peripheral-blood mononuclear cells. Colonies were genotyped to identify isogenic euploid and aneuploid iPSCs, which were differentiated into ECs for all downstream experiments. After selection for CD31 expression, baseline properties and response of cell monolayers to shear stress using a cone-plate viscometer were characterized using microscopy, qRT-PCR, RNAseq, and functional assays. We generated 45,X, and 46,XX iPSCs from one mosaic donor and successfully differentiated them into ECs. Baseline properties were not significantly different between karyotypes. Collagen gel contraction by 45,X was significantly higher than 46,XX at baseline and in response to exogenous TGF-β. Transcriptional analysis showed SNAI1, ZEB2 and other endMT-associated genes were significantly upregulated in 45,X and were partially suppressed by shear stress in 46,XX. Despite similar baseline EC phenotypes, the threshold for endMT activation appears to be lower in 45,X compared to 46,XX. Dysregulation of endMT, possibly due to chronic derepression of SNAI1, may contribute to cardiovascular disease in TS.
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Aberrant Regulation of endMT in Turner Syndrome: Implications for the Pathogenesis of Congenital Cardiovascular DiseaseWork title
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articleOpenAlex work type
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enPrimary language
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2025Year of publication
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2025-10-06Full publication date if available
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Eric Ivan Garcia Huitron, Xiaoying Zhang, Lance Babcock, K. Jane Grande‐Allen, Siddharth K. PrakashList of authors in order
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https://doi.org/10.21542/gcsp.2025.hvbte.42Publisher landing page
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diamondOpen access status per OpenAlex
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https://doi.org/10.21542/gcsp.2025.hvbte.42Direct OA link when available
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