Cell fate reprogramming using transcription factor feedback overexpression
Thesis: M. Eng., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2018.
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| Other Authors: | |
| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2018
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| Online Access: | http://hdl.handle.net/1721.1/119340 |
| _version_ | 1826191376226713600 |
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| author | Kumar, Nithin Senthur |
| author2 | Domitilla Del Vecchio. |
| author_facet | Domitilla Del Vecchio. Kumar, Nithin Senthur |
| author_sort | Kumar, Nithin Senthur |
| collection | MIT |
| description | Thesis: M. Eng., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2018. |
| first_indexed | 2024-09-23T08:54:56Z |
| format | Thesis |
| id | mit-1721.1/119340 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T08:54:56Z |
| publishDate | 2018 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/1193402019-04-10T19:43:57Z Cell fate reprogramming using transcription factor feedback overexpression Kumar, Nithin Senthur Domitilla Del Vecchio. Massachusetts Institute of Technology. Department of Mechanical Engineering. Massachusetts Institute of Technology. Department of Mechanical Engineering. Mechanical Engineering. Thesis: M. Eng., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2018. Cataloged from PDF version of thesis. Includes bibliographical references (pages 63-67). Recent advances in stem cell research has demonstrated that the fate of a terminally differentiated cell can be reverted back to pluripotency. The ability to reprogram a differentiated cell back to its undifferentiated, pluripotent state would be a significant breakthrough for regenerative medicine. For example, lost or damaged cells could be replaced by patient-specific reprogrammed cells, thus providing on-demand, compatible, high-quality cells of any required type. However, current protocols for reprogramming rely on simplified models that do not wholly capture system dynamics and on inefficient transcription factor overexpression. We study a gene regulatory network that determines the cell fate in the hematopoietic lineage and demonstrate that a deterministic model cannot capture the experimentally observed system dynamics. We also propose the use of feedback control to address inefficient reprogramming and implement two configurations of the controller on both deterministic and stochastic models of the Oct4-Nanog network. We also address practical issues such as placement of the regulator and consider the effect of inducing or constitutively producing microRNA on the protein steady-state distribution. by Nithin Senthur Kumar. M. Eng. 2018-11-28T15:43:55Z 2018-11-28T15:43:55Z 2018 2018 Thesis http://hdl.handle.net/1721.1/119340 1065526129 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 67 pages application/pdf Massachusetts Institute of Technology |
| spellingShingle | Mechanical Engineering. Kumar, Nithin Senthur Cell fate reprogramming using transcription factor feedback overexpression |
| title | Cell fate reprogramming using transcription factor feedback overexpression |
| title_full | Cell fate reprogramming using transcription factor feedback overexpression |
| title_fullStr | Cell fate reprogramming using transcription factor feedback overexpression |
| title_full_unstemmed | Cell fate reprogramming using transcription factor feedback overexpression |
| title_short | Cell fate reprogramming using transcription factor feedback overexpression |
| title_sort | cell fate reprogramming using transcription factor feedback overexpression |
| topic | Mechanical Engineering. |
| url | http://hdl.handle.net/1721.1/119340 |
| work_keys_str_mv | AT kumarnithinsenthur cellfatereprogrammingusingtranscriptionfactorfeedbackoverexpression |