Date of Award
Spring 2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Biomedical Engineering (ENAS)
First Advisor
Lin, Haifan
Abstract
Mouse germline stem cells (GSCs) play critical roles in spermatogenesis by self-renewal and differentiation into daughter spermatogonia. Like other stem cells, the proper functions of mouse GSCs are governed by a delicate regulatory network. PIWI proteins belong to the Argonaute protein family, and they act with piRNAs to control gene expression through transcriptional and post-transcriptional regulation. Extensive research has demonstrated the vital functions of PIWI proteins in germline development, stem cell maintenance, and transposon control. Despite this, the role of PIWI in mammalian GSCs remains largely unknown. MILI is one of three murine PIWI proteins. Recent study has discovered that MILI is important in regulating GSCs functions, as its mutation impairs the mitosis of GSCs. However, the molecular mechanisms are yet to be determined.In this thesis, I will describe the function and molecular mechanism of MILI in mouse GSCs. In chapter I, I briefly introduce the mammalian GSCs and PIWI subfamily proteins. In chapter II, I determine the biological function of MILI in GSCs. I find that MILI is required for GSCs proliferation. In chapter III, I explore the MILI-dependent post-transcriptional regulation in GSCs, and demonstrate that MILI positively regulates the expression of target mRNAs and such regulation may be important for GSCs functions. In chapter IV, I investigate the molecular mechanism by which MILI regulates the division of GSCs, and reveal that MILI partner with DAZL to promote GSCs proliferation via Epas1/ β-catenin pathway. In chapter V, I show MILI associates with UPF1-mediated NMD complex in GSCs, providing an entry point for future studies on MILI-dependent mRNA decay. In chapter VI, I systematically characterize the interaction between MILI and eIF3a-containing translational machinery in GSCs. Finally in chapter VII, I summarize my thesis work and present suggestions for the future research.
Recommended Citation
Wang, Yuqi, "Uncovering the Function and Molecular Mechanism of MILI in Mouse Germline Stem Cells" (2023). Yale Graduate School of Arts and Sciences Dissertations. 874.
https://elischolar.library.yale.edu/gsas_dissertations/874
