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Transcriptomic Predictors Of Infertility: Insights From Esc Under Stress And Uterine Dendritic Cells
Access Type
WSU Access
Date of Award
January 2025
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Molecular Biology and Genetics
First Advisor
Gil Mor
Second Advisor
Douglas Ruden
Abstract
This study explores the molecular mechanisms governing cellular responses to environmental stressors, with a focus on embryonic development and immune regulation. By integrating findings from embryonic stem cells (ESCs), and tissue-resident dendritic cells (uDCs) in the human endometrium, this research advances our understanding of stress impacts on developmental biology and immune function. Chapter 1 employs single-cell RNA sequencing (scRNAseq) to investigate ESC responses to varying doses of sorbitol, revealing dose-dependent transcriptomic changes and highlighting the differential susceptibility of cellular subpopulations to stress. High doses disrupt pluripotency and activate differentiation pathways, while low doses maintain stem-like characteristics. These findings emphasize the role of environmental stress in altering ESC differentiation trajectories. Chapter 2 expands on this by identifying a "pan-stress" signature across various stressors, illustrating how weak stressors maintain normal differentiation, while strong stressors lead to aberrant differentiation and disrupted regulatory networks. In Chapter 3, scRNAseq of uDCs in the human endometrium uncovers a self-renewing progenitor population, challenging the notion that uDCs are exclusively recruited from peripheral blood. This discovery offers new insights into immune regulation during reproductive processes, highlighting the roles of markers like CLEC10A and AXL in immune tolerance and implantation. Together, these chapters demonstrate the interconnectedness of stress, development, and immune regulation, with implications for reproductive health, regenerative medicine, and stress mitigation. Future research should integrate multi-omics approaches to further explore the molecular networks underlying stress adaptation and immune regulation.
Recommended Citation
Singh, Aditi, "Transcriptomic Predictors Of Infertility: Insights From Esc Under Stress And Uterine Dendritic Cells" (2025). Wayne State University Dissertations. 4215.
https://digitalcommons.wayne.edu/oa_dissertations/4215