Award Date
August 2025
Degree Type
Thesis
Degree Name
Master of Science (MS)
Department
Life Sciences
First Committee Member
Allyson Hindle
Second Committee Member
Boo Shan Tseng
Third Committee Member
Mo Weng
Fourth Committee Member
Chandrabali Bhattacharya
Number of Pages
122
Abstract
Organismal cells encounter varying conditions, including daily and potentially seasonal fluctuations in available glucose. While some species tightly regulate circulating glucose levels, others tolerate extreme fluctuations, such as frugivorous bats experiencing post-prandial hyperglycemia and hibernating mammals maintaining stable glucose through torpor and hibernation. To investigate how these species-specific strategies influence cellular responses to glucose perturbation, primary dermal fibroblasts from nine mammals – humans, rats, Egyptian fruit bats, brown bear, 13-lined ground squirrel, little brown bat, gelada, honey badger, and Bactrian camel – were exposed to hypoglycemic (2.5mM), baseline (8mM), or hyperglycemic (30mM) treatment. Cell morphology was evaluated using Cell Painting, a high-content imaging approach that labeled the nucleus, actin cytoskeleton, and ER. Morphological features, including size, shape, intensity, texture, and nuclear-to-actin ratio, were extracted using CellProfiler. Distinct species-specific remodeling patterns emerged. Glucose-sensitive species, including humans and rats, showed coordinated reductions in nuclear and cytoskeletal size under high-glucose stress, while glucose-tolerant species such as fruit bats exhibited minimal morphological disruption. To complement this phenotypic data, transcriptome analysis was performed using RNA sequencing across all glucose treatments in humans, rats, Egyptian fruit bats, little brown bats, and 13-lined ground squirrels. Differential gene expression analysis revealed conserved and species-specific patterns. Glucose-sensitive species, such as humans and rats, exhibited broad activation of inflammatory, oxidative stress, and metabolic regulatory pathways under glucose stress, whereas glucose-tolerant species like fruit bats exhibited extensive but controlled transcriptional changes consistent with metabolic flexibility. Together, these results provide a comparative framework for understanding how mammals manage glucose-induced cellular stress. The integration of morphological and transcriptomic data highlights both convergent and divergent strategies of cellular glucose regulation, offering insights into the evolutionary plasticity of metabolic homeostasis and its relevance to metabolic disorders such as diabetes.
Keywords
Biology; Cellular and Molecular; Glucose; Mammals; Microscopy; Physiology
Disciplines
Biology
File Format
Degree Grantor
University of Nevada, Las Vegas
Language
English
Repository Citation
Burke, Cassandra, "Morphological and Transcriptional Responses of Mammalian Cells to Glucose Stress" (2025). UNLV Theses, Dissertations, Professional Papers, and Capstones. 5370.
http://dx.doi.org/10.34917/39385594
Rights
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