We are trying to improve the usability of eCommons and we need your help! Please sign up here - https://forms.gle/mBwXs4zfy75wvGNE7
Library

eCommons

 

COMPARISONS OF THE PROXIMAL AND DISTAL REGIONS OF THE FALLOPIAN TUBE

Simple item page
dc.contributor.authorRose, Ian Michael
dc.contributor.chairNikitin, Alexander
dc.contributor.committeeMemberKurpios, Natasza
dc.contributor.committeeMemberDanko, Charles G.
dc.date.accessioned2021-03-15T13:31:44Z
dc.date.available2023-01-11T07:01:15Z
dc.date.issued2020-12
dc.description182 pages
dc.description.abstractOvarian/extra-uterine high-grade serous carcinoma (HGSC) is the most common and most lethal gynecological malignancy in the United States. There is now a substantial body of evidence indicating that many (and likely more than half) of HGSCs originate in the Fallopian tube. Moreover, serous tubal intraepithelial carcinomas (STICs), the putative precursor lesions to HGSC are more frequently found in the distal (closer to the ovary) Fallopian tube's epithelium (TE). This has led many to wonder what factors might be influencing the distal region of the TE to give rise to HGSC. Here, comparisons between the proximal region of the Fallopian tube (which is farther from the ovary, and evidently less inclined towards malignant transformation) and the distal region of the Fallopian tube are used to identify factors which may be promoting malignant transformation in the TE. Adult tissue stem cells (SCs) are frequently involved in malignant transformation. Previous studies suggests that the proximal and distal TE differ in the number and properties of their SCs. Inflammation associated with ovulation is also suspected of being involved in ovarian cancer's development. However, data pertaining to the human TE is sparse, and genomic data is particularly scarce. Accordingly, we isolated populations enriched for stem and differentiated epithelial cells from both proximal and distal anatomically normal Fallopian tube fragments. We then performed organoid and bulk mRNA-seq analyses aimed at identifying differences between the proximal and distal TE. Our analysis identifies heightened inflammatory signaling in distal differentiated cell enriched populations. Additionally, we observe expression of gene sets associated with HGSC and malignant disease in SC enriched populations. Applying bulk mRNA-seq to epithelial cell enabled us to identify broad patterns of gene expression across the TE. While valuable, this approach precludes analyses focused on the biology of non-epithelial cells. The use of bulk mRNA-seq also presents challenges to identifying patterns of gene expression characteristic of specific cell types. Therefore, we carried out single cell mRNA-seq using the proximal and distal Fallopian tube fragments of four more individuals, supplemented by published single cell distal TE and HGSC data. Consistent with our earlier findings, distal secretory epithelial cells display increased expression of several genes associated with NF-_B signaling.
dc.identifier.doihttps://doi.org/10.7298/tfmt-d066
dc.identifier.otherRose_cornellgrad_0058F_12296
dc.identifier.otherhttp://dissertations.umi.com/cornellgrad:12296
dc.identifier.urihttps://hdl.handle.net/1813/103223
dc.language.isoen
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleCOMPARISONS OF THE PROXIMAL AND DISTAL REGIONS OF THE FALLOPIAN TUBE
dc.typedissertation or thesis
dcterms.licensehttps://hdl.handle.net/1813/59810
thesis.degree.disciplineGenetics, Genomics and Development
thesis.degree.grantorCornell University
thesis.degree.levelDoctor of Philosophy
thesis.degree.namePh. D., Genetics, Genomics and Development

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Rose_cornellgrad_0058F_12296.pdf
Size:
16.32 MB
Format:
Adobe Portable Document Format
Download

Collections

Cornell Theses and Dissertations