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Uncovering the Function and Molecular Mechanism of MILI in Mouse Germline Stem Cells.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Uncovering the Function and Molecular Mechanism of MILI in Mouse Germline Stem Cells./
作者:
Wang, Yuqi.
面頁冊數:
1 online resource (165 pages)
附註:
Source: Dissertations Abstracts International, Volume: 85-01, Section: B.
Contained By:
Dissertations Abstracts International85-01B.
標題:
Biomedical engineering. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30311472click for full text (PQDT)
ISBN:
9798379778392
Uncovering the Function and Molecular Mechanism of MILI in Mouse Germline Stem Cells.
Wang, Yuqi.
Uncovering the Function and Molecular Mechanism of MILI in Mouse Germline Stem Cells.
- 1 online resource (165 pages)
Source: Dissertations Abstracts International, Volume: 85-01, Section: B.
Thesis (Ph.D.)--Yale University, 2023.
Includes bibliographical references
Mouse germline stem cells (GSCs) play critical role 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. However, the role of post-transcriptional factors in GSCs is under-investigated. 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 function of PIWI in mammalian GSCs is unclear. MILI is one of three murine PIWI proteins. A recent study discovered that MILI may serve as a key post-transcriptional regulator in GSCs, as its mutation impairs the mitosis and new protein synthesis of GSCs. Nonetheless, the molecular mechanisms are yet to be determined.In this thesis, I further analyze the function and molecular mechanism of MILI in mouse GSCs. In chapter I, I briefly introduce 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 GSC proliferation, but not survival or maintenance.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 that such regulation may be important for GSC functions. In chapter IV, I investigate the molecular mechanism by which MILI regulates the division of GSCs and report that MILI partners with DAZL to promote GSC proliferation via the Epas1-β-catenin pathway. In chapter V, I show that 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.
Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023
Mode of access: World Wide Web
ISBN: 9798379778392Subjects--Topical Terms:
535387
Biomedical engineering.
Subjects--Index Terms:
Molecular mechanismIndex Terms--Genre/Form:
542853
Electronic books.
Uncovering the Function and Molecular Mechanism of MILI in Mouse Germline Stem Cells.
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Mouse germline stem cells (GSCs) play critical role 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. However, the role of post-transcriptional factors in GSCs is under-investigated. 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 function of PIWI in mammalian GSCs is unclear. MILI is one of three murine PIWI proteins. A recent study discovered that MILI may serve as a key post-transcriptional regulator in GSCs, as its mutation impairs the mitosis and new protein synthesis of GSCs. Nonetheless, the molecular mechanisms are yet to be determined.In this thesis, I further analyze the function and molecular mechanism of MILI in mouse GSCs. In chapter I, I briefly introduce 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 GSC proliferation, but not survival or maintenance.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 that such regulation may be important for GSC functions. In chapter IV, I investigate the molecular mechanism by which MILI regulates the division of GSCs and report that MILI partners with DAZL to promote GSC proliferation via the Epas1-β-catenin pathway. In chapter V, I show that 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.
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