Single cell expression analysis of human cellular reprogramming
Abstract/Contents
- Abstract
- The ability to reprogram adult human cells into induced pluripotent stem cells (iPSCs) has allowed us to study development like never before. By studying the reprogramming process, we are able to dissect molecular and developmental events that give rise to all cells of the human body. Despite intense interest and research into the molecular mechanisms of reprogramming, we still lack full understand the reprogramming process itself and downstream effects on the resulting cells. What we do know is that there is a significant amount of heterogeneity in the cells that result from reprogramming and in the way that individual, otherwise homogenous, cells respond to reprogramming factors. In order to better understand the reprogramming process, I used an mRNA reprogramming technique to modulate the types and numbers of mRNAs used in an attempt to identify novel reprogramming factors. I generated a large dataset of gene expression data from single iPSCs and parental fibroblasts to uncover some of the expression patterns that define different developmental time points. This dataset includes two cell lines (fetal and adult), four developmental time points (fibroblasts, passage 0, passage 3, and passage 20 iPSCs), as well as two growth conditions (5 or 20% oxygen). Using this dataset, I was able to address critical questions about the effects of reprogramming on female cells. Female cells have a unique biology linked to X chromosome inactivation, which is required to equalize the gene expression between males and females. As this X chromosome-based epigenetic regulation is set up in early development, there has been much interest in the state of the X chromosome during the reprogramming process. Here, I show that passage 0 iPSCs maintain XCI but that these cells lose XIST expression, which is the non-coding RNA that regulated the silencing, by passage 20. These results have significant implications for the clinical translation of stem cell therapies into clinics, especially for women.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2015 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Briggs, Sharon Foley |
|---|---|
| Associated with | Stanford University, Department of Genetics. |
| Primary advisor | Baker, Julie, (Professor of genetics) |
| Thesis advisor | Baker, Julie, (Professor of genetics) |
| Thesis advisor | Fire, Andrew Zachary |
| Thesis advisor | Reijo Pera, Renee |
| Thesis advisor | Sage, Julien |
| Advisor | Fire, Andrew Zachary |
| Advisor | Reijo Pera, Renee |
| Advisor | Sage, Julien |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Sharon Foley Briggs. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2015. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2015 by Sharon Foley Briggs
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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