THE FINE BALANCE OF ESOPHAGEAL HOMEOSTASIS: THE ROLE OF UNIQUE CELLS

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Degree type
Doctor of Philosophy (PhD)
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Biochemistry and Molecular Biophysics
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Biochemistry, Biophysics, and Structural Biology
Biology
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01/01/2024
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Reyes Hueros, Raul, Antonio
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Abstract

This study explores the intricacies of cellular variability and expression in the context of invitro models of esophageal epithelial cells (EPC2-hTERT) and Barrett’s Esophagus (BE), shedding light on the diverse growth dynamics and cellular states within these systems. Esophageal epithelial cells highlighted remarkable growth variability, with approximately 10% of clones exhibiting exponential growth, while the majority displayed logistic growth patterns or halted growth due to non-proliferative cells. Through clonal tracing, mathemat- ical modeling, and cellular barcoding, we elucidated the heritability of growth tendencies and the impact of environmental conditions, such as plating density, on proliferative capa- bilities. Combining barcoding with single-cell RNA-sequencing (scRNA-seq), we identified the cellular states associated with the highly proliferative clones, which include genes in the WNT and PI3K pathways. Finally, we identified an enrichment of cells resembling the highly proliferative cell state in the proliferating healthy human esophageal epithelium. In BE, advanced spatial transcriptomics revealed a detailed cellular architecture along glan- dular structures, pinpointing various cell types including previously unidentified ones like tuft and ciliated cells. Notably, ciliated cells at the transitional zone between squamous and columnar epithelium suggest a potential role in the early stages of BE development.

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Shaffer, Sydney, M
Date of degree
2024
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