Transcription factor-mediated lineage conversion into neuronal cells
Abstract/Contents
- Abstract
- Induced pluripotent stem cells technology has introduced many possibilities for regenerative medicine as therapy can potentially be tailored to specific patients. More recently, direct reprogramming using transcription factors to convert somatic cells into neuronal cell types has further bent the paradigm that the adult cell fate is fixed. Previous studies have identified specific transcription factors that can directly generate neurons from fibroblasts. Here, we hypothesized that a different combination of transcription factors can generate specific neuronal subtypes. In particular we looked at midbrain dopamine neurons that are implicated in Parkinson's disease. We identified 5 transcription factors Ascl1, Nurr1 Lmx1a, En1, FoxA2 that can convert mouse fibroblasts into midbrain dopamine neurons. In murine and human embryonic stem cells, we identified 6 transcription factors Ascl1, Nurr1, Lmx1a, En1, FoxA2 and Pitx3, together with an exogenous supply of WNT1 protein that can generate dopamine neurons of the central nervous system fate. These dopamine neurons express midbrain-type markers, produce dopamine and exhibit electrophysiological properties akin to midbrain dopamine neurons. This study also suggests that a different combination of neuronal transcription factors might generate neurons of other subtypes, such as inhibitory or adrenergic neurons. Generation of subtype neurons could have important implications for drug studies, disease modeling and potential clinical applications.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Ng, Yi Han |
|---|---|
| Associated with | Stanford University, Department of Microbiology and Immunology. |
| Primary advisor | Wernig, Marius |
| Thesis advisor | Wernig, Marius |
| Thesis advisor | Blau, Helen M |
| Thesis advisor | Carette, Jan, 1971- |
| Thesis advisor | Sarnow, P. (Peter) |
| Advisor | Blau, Helen M |
| Advisor | Carette, Jan, 1971- |
| Advisor | Sarnow, P. (Peter) |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Yi Han Ng. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Yi Han Ng
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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