4.2 Article

The role of methylation, DNA polymorphisms and microRNAs on HLA-G expression in human embryonic stem cells

期刊

STEM CELL RESEARCH
卷 19, 期 -, 页码 118-127

出版社

ELSEVIER SCIENCE BV
DOI: 10.1016/j.scr.2017.01.005

关键词

HLA-G; hESC Promoter methylation; 3 ' UTR; MicroRNA

资金

  1. Wetenschappelijk Fonds Willy Gepts of the UZ Brussel [WFWG08-10, WFWG13-20]
  2. research committee of the Vrije Universiteit Brussel [OZR1447, 1447 BOF]
  3. Department of Hematology, Universitair Ziekenhuis Brussel (UZ Brussel)

向作者/读者索取更多资源

The human leukocyte antigen (HLA)-G gene seems to play a pivotal role in maternal tolerance to the fetus. Little is known about HLA-G expression and its molecular control during in vivo human embryogenesis. Human embryonic stem cells (hESC) provide an interesting in vitro model to study early human development. Different studies reported discrepant findings on whether HLA-G mRNA and protein are present or absent in hESC. Several lines of evidence indicate that promoter CpG methylation and 3' untranslated region (3'UTR) polymorphisms may influence HLA-G expression. We investigated how HLA-G expression is linked to the patterns of promoter methylation and explored the role of the 3'UTR polymorphic sites and their binding microRNAs on the post-transcriptional regulation of HLA-G in eight hESC lines. We showed that, while the gross expression levels of HLA-G are controlled by promoter methylation, the genetic constitution of the HLA-G 3'UTR, more specifically the 14bp insertion in combination with the + 3187A/A and + 3142G/G SNP, plays a major role in HLA-G mRNA regulation in hESC. Our findings provide a solid first step towards future work using hESC as tools for the study of early human developmental processes in normal and pregnancy-related disorders such as preeclampsia. (C) 2017 The Authors. Published by Elsevier B.V.

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