RT Journal Article
SR Electronic
T1 Sexual dimorphism in epigenomic responses of stem cells to extreme fetal growth
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 008482
DO 10.1101/008482
A1 Fabien Delahaye
A1 N. Ari Wijetunga
A1 Hye J. Heo
A1 Jessica N. Tozour
A1 Yong Mei Zhao
A1 John M. Greally
A1 Francine H. Einstein
YR 2014
UL http://biorxiv.org/content/early/2014/08/27/008482.abstract
AB 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+ hematopoietic stem/progenitor cells (HSPCs) 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. A sexually dimorphic response was found, intrauterine growth restriction (IUGR) associated with substantially greater epigenetic dysregulation in males but large for gestational age (LGA) growth affecting females predominantly. The findings are consistent with extreme fetal growth interacting with variable fetal susceptibility to influence cellular aging and metabolic characteristics through epigenetic mechanisms, potentially generating biomarkers that could identify infants at higher risk for chronic disease later in life.