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Investigating Cell State Plasticity at the Gastroesophageal Junction with Lineage Tracing in Humans / Rodrigo Alexander Gier.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Gier, Rodrigo Alexander, author.
- Language:
- English
- Subjects (All):
- Bioengineering.
- Cellular biology.
- Endocrinology.
- Genetics.
- Bioengineering--Penn dissertations.
- Penn dissertations--Bioengineering.
- Local Subjects:
- Bioengineering.
- Cellular biology.
- Endocrinology.
- Genetics.
- Bioengineering--Penn dissertations.
- Penn dissertations--Bioengineering.
- Physical Description:
- 1 online resource (142 pages)
- Distribution:
- Ann Arbor : ProQuest Dissertations & Theses, 2023
- Contained In:
- Dissertations Abstracts International 85-08B.
- Place of Publication:
- [Philadelphia, Pennsylvania] : University of Pennsylvania, 2022.
- Language Note:
- English
- Summary:
- Barrett's esophagus is a common type of metaplasia and a precursor of esophageal adenocarcinoma. However, the cell states and lineage connections underlying the origin, maintenance, and progression of Barrett's esophagus have not been resolved in humans. To address this, we performed single-cell lineage tracing and transcriptional profiling of patient cells isolated from metaplastic and healthy tissue. Our analysis unexpectedly revealed that the squamous esophagus and gastric cardia contained cells belonging to common lineages that also included transitional basal progenitor cells; both esophageal and gastric tissues were also related to Barrett's esophagus. Barrett's esophagus was polyclonal, with lineages that contained all progenitor and differentiated cell types. In contrast, precancerous dysplastic foci were initiated by the expansion of a single molecularly aberrant Barrett's esophagus clone. Together, these findings provide a comprehensive view of the cell dynamics of Barrett's esophagus, linking cell states along the full disease trajectory, from its origin to cancer.
- Notes:
- Source: Dissertations Abstracts International, Volume: 85-08, Section: B.
- Advisors: Shaffer, Sydney M.; Committee members: Camara, Pablo G.; Hamilton, Kathryn E.; Hughes, Alex J.
- Department: Bioengineering.
- Ph.D. University of Pennsylvania 2023.
- Local Notes:
- School code: 0175
- ISBN:
- 9798381472165
- Access Restriction:
- Restricted for use by site license.
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