Transcriptional and functional convergence of coronary endothelial lineages in mouse and human
Abstract/Contents
- Abstract
- Coronary blood vessels comprise the arteries, veins and capillaries that supply the heart. In mice, the endothelial cells (ECs) that form the inner lining of these vessels are derived primarily from two lineages during embryonic development. The first lineage comes from the endocardium (Endo), the layer of cells lining the inside of the heart chambers. The second lineage comes from the endothelium of the sinus venosus (SV), the major inflow tract of the developing heart. Although these two lineages are known to contribute to complementary regions of the heart during both development and adulthood, it is unknown whether there is any difference in their function or whether they retain any transcriptional markers of their origins. In addition, it is unknown whether ECs in human hearts also originate from the same sources. In order to address these questions, I combined lineage tracing of Endo-derived ECs in murine hearts at various stages with single-cell RNA sequencing. I discovered that while Endo- and SV-derived ECs can be transcriptionally distinguished at e12, they had equivalent transcriptional patterns at e17.5. Additionally, at e17.5 capillary ECs segregated into two populations based on the influences of blood flow and hypoxia. On the other hand, adult ECs from both lineages were transcriptionally homogenous with respect to both lineage and location, and responded similarly to ischemia-reperfusion injury. Finally, developing human hearts contained capillary ECs in similar cell states as e17.5 mouse hearts, indicating that mouse and human coronary development follow similar trajectories.
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 | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Phansalkar, Ragini |
|---|---|
| Degree supervisor | Red-Horse, Kristy |
| Thesis advisor | Red-Horse, Kristy |
| Thesis advisor | Baker, Julie |
| Thesis advisor | Bhatt, Ami (Ami Siddharth) |
| Thesis advisor | Kundaje, Anshul, 1980- |
| Degree committee member | Baker, Julie |
| Degree committee member | Bhatt, Ami (Ami Siddharth) |
| Degree committee member | Kundaje, Anshul, 1980- |
| Associated with | Stanford University, Department of Genetics |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Ragini Phansalkar. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/vh355ph5705 |
Access conditions
- Copyright
- © 2021 by Ragini Phansalkar
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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