Elucidating the transcriptomic dynamics in human embryonic development

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 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.

Date of Award	2023
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Danny Chi Yeu LEUNG (Supervisor)