Abstract
CXCL14 is a chemokine that has previously been implicated in insulin resistance in mice. In humans, the role of CXCL14 in metabolic processes is not well established, and we sought to determine whether CXCL14 is a risk susceptibility gene important in fetal programming of metabolic disease. For this purpose, we investigated whether CXCL14 is differentially regulated in human umbilical cords of infants with varying birth weights. We found an elevated expression of CXCL14 in human low birth weight (LBW) cords, as well as in cords from nutritionally restricted Macaca fascicularis macaques. To further analyze the regulatory mechanisms underlying the expression of CXCL14, we examined CXCL14 in umbilical cord-derived mesenchymal stem cells (MSCs) that provide an in vitro cell-based system amenable to experimental manipulation. Using both whole frozen cords and MSCs, we determined that site-specific CpG methylation in the CXCL14 promoter is associated with altered expression, and that changes in methylation are evident in LBW infant-derived umbilical cords that may indicate future metabolic compromise through CXCL14.
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Acknowledgements
We are grateful for the expert technical assistance of Rachel Chew, Tan Li Hua and Yhee Cheng Chng. We thank Professor Kenneth Kwek and the GUSTO study group for enabling the collection of umbilical cord tissue. This work is supported by the Translational Clinical Research (TCR) Flagship Program on Developmental Pathways to Metabolic Disease funded by the National Research Foundation (NRF) and administered by the National Medical Research Council (NMRC), Singapore (NMRC/TCR/004-NUS/2008). SICS Investigators are supported through Agency for Science Technology and Research (A*STAR) funding.
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Cheong, C., Chng, K., Lim, M. et al. Alterations to DNA methylation and expression of CXCL14 are associated with suboptimal birth outcomes. J Hum Genet 59, 504–511 (2014). https://doi.org/10.1038/jhg.2014.63
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DOI: https://doi.org/10.1038/jhg.2014.63
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