Author ORCID Identifier

0000-0001-6099-1879

Date of Graduation

5-2020

Document Type

Dissertation (PhD)

Program Affiliation

Cancer Biology

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Jichao Chen, Ph.D.

Committee Member

Jonathan Davies, M.D.

Committee Member

Randy Johnson, Ph.D.

Committee Member

Seyed Javad Moghaddam, M.D.

Committee Member

Nicholas Navin, Ph.D.

Abstract

The mammalian lung is a complex system of specialized cell types with precise spatial organization designed to cooperate to perform gas exchange. These cell types together coordinate organ development, homeostasis, and repair after injury through signals either presented or secreted, known as ligands, to be received by receptors on the surface of another, or in some cases, the same cell. The alveolar region of the lung, the primary region of gas exchange, responds to various types of injuries with different lung repair mechanisms. In order to explore how the various cell types in the lung communicate to drive tissue repair after Sendai virus infection-induced damage, we developed a single-cell interactome method to uncover novel interactions between epithelial and non-epithelial cell types. Our interactome method employs a numeric representation of ligand-receptor interactions and identifies known and potentially new interactions as outliers. Application of our interactome method to compare control and Sendai virus-infected lung tissue, we uncovered a signaling relationship between alveolar type 1 (AT1) cells and capillary endothelial cells. We also applied our interactome to a hyperoxia model for bronchopulmonary dysplasia, another injury model affecting a majority of lung cell types. In concert with our sequencing approaches to study cellular interactions, we surveyed Sendai virus-infected lung tissue to understand the path by which airway basal-like cells migrate into the regions of alveolar damage, a documented but not well understood phenomenon. We discovered an association between AT1 cells and these invading airway cells. This thesis is an exploration of the complex relationships of the cell types that make up the lung and how they coordinate the mammalian lung’s response to injury and tissue repair.

Keywords

single-cell RNA-seq, ligand-receptor interaction, bioinformatics, lung viral injury, cell biology

Available for download on Saturday, May 01, 2021

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