Functional genomic analysis identifies novel regulators of germline development using flatworm models
Abstract/Contents
- Abstract
- Schistosomes are parasitic flatworms causing one of the most prevalent neglected tropical diseases, schistosomiasis, from which over 250 million people are suffering. With a further 800 million at risk of infection, schistosomiasis imposes a global socioeconomic burden comparable to that of tuberculosis, HIV/AIDS, and malaria. Only a single, partially effective drug is available to treat the disease. These parasites have high fecundity and their eggs are both the transmissible agents and the cause of the infection-associated pathology. Despite the biomedical significance, molecular mechanisms that regulate schistosome reproduction and germline development are only now being understood. Through single-cell RNA sequencing and functional genomic analysis, we first discover that the schistosome germline stem cells (GSCs) derive from a population of somatic stem cells in juvenile parasites. This cell lineage expresses a schistosome specific factor, which we name eled. Through loss-of-function studies, we find that eled prevents the premature differentiation of GSCs. Second, we identify a gene regulatory circuit that balances the output of proliferation and differentiation of the schistosome male GSCs. This program is controlled by onecut, a homeobox transcription factor, and boule, a highly conserved mRNA binding protein essential for germline development in many animals. The germline specific expression of these regulators is conserved in the planarian, the free-living evolutionary cousin of the schistosome, but the function of onecut and boule has been modified to support GSC maintenance. Altogether, my thesis provides important insights to understand the fate regulation and evolutionary adaptation of germline development.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Li, Pengyang |
|---|---|
| Degree supervisor | Wang, Bo, (Computer systems engineer) |
| Thesis advisor | Wang, Bo, (Computer systems engineer) |
| Thesis advisor | Garten, Matthias |
| Thesis advisor | Prakash, Manu |
| Degree committee member | Garten, Matthias |
| Degree committee member | Prakash, Manu |
| Associated with | Stanford University, Department of Bioengineering |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Pengyang Li. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/mv059st0425 |
Access conditions
- Copyright
- © 2022 by Pengyang Li
- License
- This work is licensed under a Creative Commons Attribution 3.0 Unported license (CC BY).
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