Epigenetic regulation of placenta-specific 8 contributes to altered function of endothelial colony-forming cells exposed to intrauterine gestational diabetes mellitus

Emily K. Blue, Breann M. Sheehan, Zia V. Nuss, Frances A. Boyle, Caleb M. Hocutt, Cassandra R. Gohn, Kaela M. Varberg, Jeanette McClintick, Laura Haneline

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Intrauterine exposure to gestational diabetes mellitus (GDM) is linked to development of hypertension, obesity, and type 2 diabetes in children. Our previous studies determined that endothelial colony-forming cells (ECFCs) from neonates exposed to GDM exhibit impaired function. The current goals were to identify aberrantly expressed genes that contribute to impaired function of GDM-exposed ECFCs and to evaluate for evidence of altered epigenetic regulation of gene expression. Genome-wide mRNA expression analysis was conducted on ECFCs from control and GDM pregnancies. Candidate genes were validated by quantitative RT-PCR and Western blotting. Bisulfite sequencing evaluated DNA methylation of placenta-specific 8 (PLAC8). Proliferation and senescence assays of ECFCs transfected with siRNA to knockdown PLAC8 were performed to determine functional impact. Thirty-eight genes were differentially expressed between control and GDM-exposed ECFCs. PLAC8 was highly expressed in GDM-exposed ECFCs, and PLAC8 expression correlated with maternal hyperglycemia. Methylation status of 17 CpG sites in PLAC8 negatively correlated with mRNA expression. Knockdown of PLAC8 in GDMexposed ECFCs improved proliferation and senescence defects. This study provides strong evidence in neonatal endothelial progenitor cells that GDM exposure in utero leads to altered gene expression and DNA methylation, suggesting the possibility of altered epigenetic regulation.

Original languageEnglish (US)
Pages (from-to)2664-2675
Number of pages12
JournalDiabetes
Volume64
Issue number7
DOIs
StatePublished - Jul 1 2015

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Gestational Diabetes
Epigenomics
Placenta
DNA Methylation
Genes
Messenger RNA
Cell Aging
Gene Expression Regulation
Hyperglycemia
Type 2 Diabetes Mellitus
Methylation
Small Interfering RNA
Obesity
Western Blotting
Mothers
Cell Proliferation
Newborn Infant
Genome
Hypertension
Gene Expression

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Epigenetic regulation of placenta-specific 8 contributes to altered function of endothelial colony-forming cells exposed to intrauterine gestational diabetes mellitus. / Blue, Emily K.; Sheehan, Breann M.; Nuss, Zia V.; Boyle, Frances A.; Hocutt, Caleb M.; Gohn, Cassandra R.; Varberg, Kaela M.; McClintick, Jeanette; Haneline, Laura.

In: Diabetes, Vol. 64, No. 7, 01.07.2015, p. 2664-2675.

Research output: Contribution to journalArticle

Blue, Emily K. ; Sheehan, Breann M. ; Nuss, Zia V. ; Boyle, Frances A. ; Hocutt, Caleb M. ; Gohn, Cassandra R. ; Varberg, Kaela M. ; McClintick, Jeanette ; Haneline, Laura. / Epigenetic regulation of placenta-specific 8 contributes to altered function of endothelial colony-forming cells exposed to intrauterine gestational diabetes mellitus. In: Diabetes. 2015 ; Vol. 64, No. 7. pp. 2664-2675.
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