Modeling human biology and complex diseases with iPSCs
Abstract/Contents
- Abstract
- Human induced pluripotent stem cells (iPSCs) have been widely acknowledged in recent years as a model system for studying human disease and development. As part of my first project, we constructed a high-resolution regulatory atlas of the developing human fetal heart, defining important regulatory regions, such as enhancers, essential to cardiogenesis. Using a new deep learning model, we identified cell-type-specific de novo variants in predicted fetal human heart enhancers. We further used in vitro differentiated endothelial cells to validate the regulatory impact of a putative cell-type-specific enhancer predicted to harbor a deleterious congenital heart disorder (CHD) mutation. As part of my second project, we have created primate pluripotent stem cell-derived cardiomyocytes that mimic fetal cardiomyocytes in vitro to identify hundreds of ERV transcripts, including those regulated by TBX5. In particular, most of the significant RNAs found in primate fetal cardiomyocytes are located in BANCR, which is a long non-coding RNA (lncRNA) that is exclusively expressed from fetal cardiomyocytes. Based on functional studies, it has been demonstrated that BANCR promotes cardiomyocyte migration in vitro as well as ventricular enlargement in vivo. Our studies suggest that recently evolved TE loci like BANCR may serve as potent de novo regulatory elements capable of controlling developmental processes that can be studied with a pluripotent stem cell model.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Ameen, Mohamed |
|---|---|
| Degree supervisor | Wang, Kevin K. W |
| Thesis advisor | Wang, Kevin K. W |
| Thesis advisor | Bhutani, Nidhi |
| Thesis advisor | Kundaje, Anshul, 1980- |
| Thesis advisor | Morrison, Ashby J |
| Degree committee member | Bhutani, Nidhi |
| Degree committee member | Kundaje, Anshul, 1980- |
| Degree committee member | Morrison, Ashby J |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Cancer Biology Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Mohamed Ameen. |
|---|---|
| Note | Submitted to the Cancer Biology Program. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/pq334sz0147 |
Access conditions
- Copyright
- © 2023 by Mohamed Ameen
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