Sexual dimorphism in epigenomic responses of stem cells to extreme fetal growth

Fabien Delahaye, N. Ari Wijetunga, Hye J. Heo, Jessica N. Tozour, Yong Mei Zhao, John M. Greally, Francine H. Einstein

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Extreme fetal growth is associated with increased susceptibility to a range of adult diseases through an unknown mechanism of cellular memory. We tested whether heritable epigenetic processes in long-lived CD34+ haematopoietic stem/progenitor cells showed evidence for re-programming associated with the extremes of fetal growth. Here we show that both fetal growth restriction and over-growth are associated with global shifts towards DNA hypermethylation, targeting cis-regulatory elements in proximity to genes involved in glucose homeostasis and stem cell function. We find a sexually dimorphic response; intrauterine growth restriction is associated with substantially greater epigenetic dysregulation in males, whereas large for gestational age growth predominantly affects females. The findings are consistent with extreme fetal growth interacting with variable fetal susceptibility to influence cellular ageing and metabolic characteristics through epigenetic mechanisms, potentially generating biomarkers that could identify infants at higher risk for chronic disease later in life.

Original languageEnglish (US)
Article number5187
JournalNature communications
Volume5
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Delahaye, F., Wijetunga, N. A., Heo, H. J., Tozour, J. N., Zhao, Y. M., Greally, J. M., & Einstein, F. H. (2014). Sexual dimorphism in epigenomic responses of stem cells to extreme fetal growth. Nature communications, 5, [5187]. https://doi.org/10.1038/ncomms6187