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Dynamic Behavior and Lineage Plasticity of the Pulmonary Venous Endothelium Joanna Wong

Dissertations & Theses @ University of Pennsylvania Available online

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Format:
Book
Thesis/Dissertation
Author/Creator:
Wong, Joanna, author.
Contributor:
University of Pennsylvania. Cell and Molecular Biology., degree granting institution.
Language:
English
Subjects (All):
Cellular biology.
Physiology.
Molecular biology.
Behavioral psychology.
0379.
0307.
0384.
0719.
Local Subjects:
Cellular biology.
Physiology.
Molecular biology.
Behavioral psychology.
0379.
0307.
0384.
0719.
Physical Description:
1 electronic resource (114 pages)
Contained In:
Dissertations Abstracts International 86-12B
Place of Publication:
Ann Arbor : ProQuest Dissertations and Theses, 2025
Language Note:
English
Summary:
Repair of the pulmonary vascular bed and the origin of new vasculature remains underexplored despite the critical necessity to meet oxygen demands after injury. Given their critical role in angiogenesis in other settings, we investigated the role of venous endothelial cells in endothelial regeneration after adult lung injury. Using single cell transcriptomics, we identified the norepinephrine transporter Slc6a2 as a marker of pulmonary venous endothelial cells and targeted that locus to generate a venous-specific, inducible Cre mouse line. Contributions of the venous endothelial cells to angiogenesis were examined during postnatal development, adult viral injury, and adult hyperoxia injury. Remarkably, we observed that venous endothelial cells proliferate into the adjacent capillary bed upon influenza injury and hyperoxia injury, but not during normal postnatal development. Imaging analysis demonstrated that venous endothelial cells exhibit the ability to proliferate and differentiate into general capillary and CAR4 expressing aerocyte capillary endothelial cells after infection, thus contributing to repair of the capillary plexus vital for gas exchange. Single cell transcriptomic analysis of Slc6a2-traced cells confirmed these observations, with progeny exhibiting significant loss of venous identity and gain of capillary marker expression upon injury resolution. Our studies thus establish that venous endothelial cells exhibit demonstrable progenitor capacity upon respiratory viral injury and sterile injury, contributing to repair of the alveolar capillary bed responsible for pulmonary function
Notes:
Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
Advisors: Vaughan, Andrew E. Committee members: Frank, David B.; Mangalmurti, Nilam; Siekmann, Arndt F.; Shin, Sunny
Ph.D. University of Pennsylvania 2025
Local Notes:
School code: 0175
ISBN:
9798280762374
Access Restriction:
Restricted for use by site license

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