Intrinsic and extrinsic signals modulate planarian stem cell fate decisions
Abstract/Contents
- Abstract
- Regeneration is a process that requires tightly regulated proliferation, differentiation, and tissue remodeling. Classical model organisms such as C. elegans, D. melanogaster, and M. musculus have limited regenerative capabilities therefore we present the freshwater planarian Schmidtea mediterranea, which provides an ideal system to study the role of stem cells in regeneration. This immortal adult organism boasts excellent regenerative capabilities driven by a stem cell population called neoblasts. The neoblast population is the only mitotically active cell type in planarians and can be easily manipulated without concern for embryonic requirements. This unique model also allows for the study of human embryonic stem cell genes in a simpler in vivo system. Thus S. mediterranea offers the opportunity to accelerate the studies and understanding of stem cell biology and regeneration in the environment of a living organism. GATA transcription factors are DNA binding proteins that are well-known master regulators of development. Through the activation and repression of transcription, these factors direct cellular differentiation toward lineage specification. Here we used loss-of-function experiments to understand the role of the GATA4/5/6 subfamily in the differentiation of neoblasts. S. mediterranea has a single homolog of mammalian GATA-4, -5, and -6, Smed-gata4/5/6, which is expressed primarily in the planarian intestine and in some neoblasts. Smed-gata4/5/6 knockdown results in perturbed homeostasis and regeneration, eventually leading to planarian death. Loss of Smed-gata4/5/6 disrupts intestinal differentiation and also affects non-intestinal lineages. During late time points of regeneration, Smed-gata4/5/6 loss leads to decreased neoblast proliferation and gene expression of neoblast subpopulations. These data support the conserved role of Smed-gata4/5/6 in intestinal differentiation and indicate the intestine may act as a neoblast niche. Our preliminary work on Experimental Evolution through irradiation exposure shows a sub-lethal dose of irradiation eliminates neoblast expression after 24 hours and expression recovery occurs after 3-4 weeks. This demonstrates S. mediterranea is a malleable model organism that can be used to study the link between regeneration and cancer.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Flores, Natasha Mahealani |
|---|---|
| Associated with | Stanford University, Cancer Biology Program. |
| Primary advisor | Sage, Julien |
| Thesis advisor | Sage, Julien |
| Thesis advisor | Giaccia, Amato J |
| Thesis advisor | Kim, Stuart |
| Thesis advisor | Morrison, Ashby J |
| Advisor | Giaccia, Amato J |
| Advisor | Kim, Stuart |
| Advisor | Morrison, Ashby J |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Natasha Mahealani Flores. |
|---|---|
| Note | Submitted to the Program in Cancer Biology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Natasha Mahealani Flores
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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