title: Alterations to DNA methylation and expression of CXCL14 are associated with suboptimal birth outcomes.
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.
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Clara Y
authors.initials: CY
authors.lastname: Cheong
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Keefe
authors.initials: K
authors.lastname: Chng
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Mei Kee
authors.initials: MK
authors.lastname: Lim
authors.affiliation: Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Ajith I
authors.initials: AI
authors.lastname: Amrithraj
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Roy
authors.initials: R
authors.lastname: Joseph
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Rami
authors.initials: R
authors.lastname: Sukarieh
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chee Tan
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Louiza
authors.initials: L
authors.lastname: Chan
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Jun Hao
authors.initials: JH
authors.lastname: Tan
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Joanna D
authors.initials: JD
authors.lastname: Holbrook
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Meaney
authors.affiliation: 1] Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore [2] Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Yap
authors.initials: Y
authors.lastname: Seng Chong
authors.affiliation: 1] Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore [2] Liggins Institute, University of Auckland, Auckland, New Zealand.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Gluckman
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Walter
authors.initials: W
authors.lastname: Stünkel
mesh_terms: D000328:Adult; D000818:Animals; D031204:Caloric Restriction; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007230:Infant, Low Birth Weight / Q000378:metabolism*; D007231:Infant, Newborn; D008252:Macaca fascicularis / Q000235:genetics; D008297:Male; D008423:Maternal Age; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014470:Umbilical Cord / Q000166:cytology / Q000378:metabolism
chemical_list: C118056:CXCL14 protein, human; D019743:Chemokines, CXC
references.citation: Vitam Horm. 2009;80:107-23
references.pmid: 19251036
references.citation: Hum Reprod. 2014 Oct 10;29(10):2287-301
references.pmid: 25129543
references.citation: J Exp Med. 2001 Sep 17;194(6):855-61
references.pmid: 11561000
references.citation: Biomed Res. 2010 Apr;31(2):123-31
references.pmid: 20460740
references.citation: Diabetes. 2011 May;60(5):1528-34
references.pmid: 21471513
references.citation: PLoS One. 2010 Apr 23;5(4):e10321
references.pmid: 20428232
references.citation: Environ Health. 2012 Jun 27;11:42
references.pmid: 22715989
references.citation: Reprod Biomed Online. 2010 Sep;21(3):391-401
references.pmid: 20638335
references.citation: Oncogene. 2010 Sep 16;29(37):5159-70
references.pmid: 20562917
references.citation: Nat Rev Endocrinol. 2012 Nov;8(11):689-92
references.pmid: 22987159
references.citation: Curr Stem Cell Res Ther. 2013 Mar;8(2):144-55
references.pmid: 23279098
references.citation: Horm Res. 2006;65 Suppl 3:5-14
references.pmid: 16612108
references.citation: Semin Fetal Neonatal Med. 2004 Oct;9(5):419-25
references.pmid: 15691778
references.citation: Int J Gynaecol Obstet. 2011 Nov;115 Suppl 1:S3-5
references.pmid: 22099437
references.citation: J Biochem. 2012 May;151(5):469-76
references.pmid: 22437940
references.citation: J Clin Endocrinol Metab. 2008 Oct;93(10):3804-9
references.pmid: 18628518
references.citation: Birth Defects Res C Embryo Today. 2011 Mar;93(1):12-8
references.pmid: 21425438
references.citation: Curr Cancer Drug Targets. 2013 May;13(4):379-99
references.pmid: 23517596
references.citation: Cancer Res. 2010 Jun 1;70(11):4394-401
references.pmid: 20460540
references.citation: PLoS One. 2012;7(7):e39744
references.pmid: 22808055
references.citation: J Biol Chem. 2007 Oct 19;282(42):30794-803
references.pmid: 17724031
references.citation: Biochem Biophys Res Commun. 2007 Dec 28;364(4):1037-42
references.pmid: 17971304
references.citation: Int J Epidemiol. 2014 Oct;43(5):1401-9
references.pmid: 23912809
references.citation: Immunity. 2005 Sep;23(3):331-42
references.pmid: 16169505
references.citation: Lancet. 1993 Apr 10;341(8850):938-41
references.pmid: 8096277
references.citation: Comp Med. 2011 Dec;61(6):514-26
references.pmid: 22330579