Behavioral and genetic characteristics of intestinal cell lineages in health and disease
Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2013.
| Váldodahkki: | |
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| Eará dahkkit: | |
| Materiálatiipa: | Oahppočájánas |
| Giella: | eng |
| Almmustuhtton: |
Massachusetts Institute of Technology
2013
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| Fáttát: | |
| Liŋkkat: | http://hdl.handle.net/1721.1/80254 |
| _version_ | 1826200319310168064 |
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| author | Kung, Kevin Su Yau |
| author2 | Alexander van Oudenaarden and Scott Manalis. |
| author_facet | Alexander van Oudenaarden and Scott Manalis. Kung, Kevin Su Yau |
| author_sort | Kung, Kevin Su Yau |
| collection | MIT |
| description | Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2013. |
| first_indexed | 2024-09-23T11:34:38Z |
| format | Thesis |
| id | mit-1721.1/80254 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T11:34:38Z |
| publishDate | 2013 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/802542019-04-11T11:32:09Z Behavioral and genetic characteristics of intestinal cell lineages in health and disease Kung, Kevin Su Yau Alexander van Oudenaarden and Scott Manalis. Massachusetts Institute of Technology. Department of Biological Engineering. Massachusetts Institute of Technology. Department of Biological Engineering. Biological Engineering. Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2013. Cataloged from PDF version of thesis. Includes bibliographical references (p. 68-76). The intestinal crypt is a highly dynamic system, as the entire epithelium is constantly turned over and renewed by the proliferative stem cells located at the bottom of the crypt. While this system is crucial for nutrient absorption, any derangements in the proliferative cells can quickly lead to cancer. In this thesis, we sought to better understand the behavioral and genetic characteristics of the different cell types along the intestinal crypt, in a mouse model. We first attempted to quantify the migration velocities and proliferative rates at a single-cell level using 5-ethynol-2'-deoxyuridine (EdU) pulse-chase labeling. While we observed marked differences in the proliferation rates between the absorptive and secretory lineages (the former is faster), our experimental setup was unable to resolve any possible differences in migratory behaviors. We then turned our attention to quantifying the spatial expression patterns of selected transcripts in the intestinal crypt, both in wildtype and in an inducible APC-loss cancer model. We were able to show that the transcript expression profiles of key differentiation and proliferation markers (Creb313, Gob5, Ki-67, cMyc), as well as the ephrin signaling (EphB2 and EphrinBl) were significantly altered in the early stages (7 days) of adenoma formation. A more detailed analysis also separated this derangement in terms of extrinsic factors (e.g. altered cell composition along the crypt) and intrinsic factors (e.g. inherent change of cellular expression profile after APC loss). What is particularly interesting is that even differentiated cells in adenomas can exhibit such derangements. Our hypothesis to explain this observation is that these differentiated cells actually come from transformed stem cells. To test this hypothesis, we needed to verify that these cells indeed have excision at the Apc locus. After several approaches involving both single-molecule fluorescent in situ hybridization and quantitative polymerase chain reaction (PCR), the results were ultimately inconclusive. However, we propose several additional approaches that this hypothesis can be verified, and if verified, some biologically significant questions that can be addressed regarding the early dynamics of stem cells in intestinal cancer development. by Kevin Su Yau Kung. S.M. 2013-08-22T19:02:07Z 2013-08-22T19:02:07Z 2013 2013 Thesis http://hdl.handle.net/1721.1/80254 853452053 eng MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission. http://dspace.mit.edu/handle/1721.1/7582 106 p. application/pdf Massachusetts Institute of Technology |
| spellingShingle | Biological Engineering. Kung, Kevin Su Yau Behavioral and genetic characteristics of intestinal cell lineages in health and disease |
| title | Behavioral and genetic characteristics of intestinal cell lineages in health and disease |
| title_full | Behavioral and genetic characteristics of intestinal cell lineages in health and disease |
| title_fullStr | Behavioral and genetic characteristics of intestinal cell lineages in health and disease |
| title_full_unstemmed | Behavioral and genetic characteristics of intestinal cell lineages in health and disease |
| title_short | Behavioral and genetic characteristics of intestinal cell lineages in health and disease |
| title_sort | behavioral and genetic characteristics of intestinal cell lineages in health and disease |
| topic | Biological Engineering. |
| url | http://hdl.handle.net/1721.1/80254 |
| work_keys_str_mv | AT kungkevinsuyau behavioralandgeneticcharacteristicsofintestinalcelllineagesinhealthanddisease |