THESIS
2023
1 online resource (x, 63 pages) : illustrations (chiefly color)
Abstract
This study aims to investigate epigenetic regulation and the role of non-coding sequences
during human embryogenesis, which, despite extensive study, remain enigmatic
due to the limited access to human embryonic tissues. The project employs clinical data and
in vitro embryonic stem cell models to comprehensively profile of transcriptomic and epigenomic
changes, particularly focusing on the non-coding regions. The class of non-coding
elements of interest is human endogenous retroviruses (HERVs), which account for approximately
8% of the human genome. While specific subfamilies of HERVs are known to be
highly expressed during early embryogenesis and are imperative for maintaining pluripotency,
their precise roles in cellular differentiation have not been deciphered. Addressing
this, the f...[
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This study aims to investigate epigenetic regulation and the role of non-coding sequences
during human embryogenesis, which, despite extensive study, remain enigmatic
due to the limited access to human embryonic tissues. The project employs clinical data and
in vitro embryonic stem cell models to comprehensively profile of transcriptomic and epigenomic
changes, particularly focusing on the non-coding regions. The class of non-coding
elements of interest is human endogenous retroviruses (HERVs), which account for approximately
8% of the human genome. While specific subfamilies of HERVs are known to be
highly expressed during early embryogenesis and are imperative for maintaining pluripotency,
their precise roles in cellular differentiation have not been deciphered. Addressing
this, the first objective of the project involved utilizing RNA sequencing data from totipotent
and pluripotent cell lines as well as embryonic tissues to elucidate the roles of HERVs in
cellular differentiation during early embryonic development. The results demonstrated that
HERV-H and LTR12C subfamilies are preferentially enriched in the totipotent state. The
second objective of this project focused on investigating the molecular dysfunction associated
with selective intrauterine growth restriction (sIUGR), a condition characterized by an uneven share of placental territories in monochorionic twin pregnancies. Through RNA
sequencing, differential gene expression was observed between the normal and growth-restricted
sides of the placenta in sIUGR samples. Further analysis using Gene Ontology
(GO) term enrichment on upregulated genes indicated that type III sIUGR is notably enriched
with terms associated with vascular endothelial growth. In summary, this thesis
highlights the potential role of HERV subfamilies in totipotency and provides insights into
the molecular underpinnings of sIUGR.
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