Dissertation/Thesis Abstract

A Drosophila RNAi Screen Identifies Protein Networks Essential for Germline Stem Cell Maintenance and Differentiation
by Sanchez, Carlos, Ph.D., New York University, 2016, 231; 10139638
Abstract (Summary)

The unique ability of stem cells to differentiate into at least one type of cell and to self-renew have made them popular entities in the therapeutic field because of the promise that stem cells can be used as replacement therapies to cure diseases such as diabetes, Parkinson’s disease or spinal cord injuries. Complex regulatory networks regulate stem cell behavior and contributions to tissue growth, repair, and homeostasis. Over the past few years there have been extensive studies in different model organisms to help decipher how stem cells control the mechanisms of self-maintenance and differentiation. Although much progress has been made, a full understanding of the networks controlling stem cell self-renewal and differentiation has not yet been realized.

The Drosophila female ovary has been widely used as a model system to study stem cells. The genetic tools available in the fly and the ability to visually analyze each stage of development allows for careful study of germline stem cells (GSC) and their progeny from undifferentiated to differentiated states. To systematically dissect these networks and identify their components, we performed an unbiased, transcriptome-wide in vivo RNAi screen in female GSCs. Based on characterized cellular defects, we classified 646 identified genes into phenotypic and functional groups and unveiled a comprehensive set of networks regulating GSC maintenance, survival, and differentiation. This analysis revealed an unexpected role for the mitochondrial ATP synthase in cristae maturation during GSC differentiation and a role for ribosomal assembly factors in controlling stem cell cytokinesis. Our data also shows that the transition from self-renewal to differentiation relies on enhanced ribosome biogenesis accompanied by increased protein synthesis. Moreover, we identified a novel factor, spenito, required for GSC differentiation that acts in the sex determination pathway. Collectively, the genes identified likely contribute to the majority of pathways involved in ovarian GSC maintenance and differentiation. Future research can now aim at connecting these extensive genetic networks in order to generate an integrated regulation protocol for stem cell homeostasis.

Indexing (document details)
Advisor: Lehmann, Ruth
Commitee: Bach, Erika, Nance, Jeremy, Ohlstein, Benjamin, Skolnik, Edward
School: New York University
Department: Basic Medical Science
School Location: United States -- New York
Source: DAI-B 78/01(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Biology, Cellular biology, Developmental biology
Keywords: Development, Drosophila, Genetics, Germline, RNAi, Stem cells
Publication Number: 10139638
ISBN: 978-1-339-95123-2
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