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Full text release has been delayed at the author's request until August 18, 2025

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SINGLE-CELL GENOMICS IDENTIFIES DIABETES-RELEVANT GENES IN HUMAN PANCREATIC ISLETS

Gu, Anniya
http://orcid.org/0000-0002-2371-1214
http://rave.ohiolink.edu/etdc/view?acc_num=case1691008840252809

Abstract Details

2023, Doctor of Philosophy, Case Western Reserve University, Genetics.
Type II Diabetes (T2D) is a metabolic disorder characterized by dysfunction of insulin-producing β cells in the pancreatic islet. The pancreas is a very heterogeneous tissue with both endocrine and exocrine cell-types. As such, single-cell sequencing technologies are a powerful tool to allow dissection of cell-type differences as well as heterogeneity within the same cell type. We utilized a single-cell multiomics approach to identify T2D-relevant disease genes in pancreatic islets. First, we developed a framework to integrate single-cell transcriptome, single-nuclei chromatin accessibility, and cell-type specific 3D genome profiles from human islets. We identified T2D-associated β cell heterogeneity driven by a transcription factor, HNF1A, at both the transcriptome and epigenome levels. Second, we identified key differences between prediabetic and diabetic β cell states. We further characterized obesity and aging profiles in human islets including a sex dimorphic response in obese states. Finally, we identified a T2D-associated disease signature in pancreatic stellate cells (PSCs) and propose a potential mechanism for PSC-β crosstalk. Overall, our study demonstrates the powerful applications of single-cell genomics technologies to identify novel biological and disease pathways.
Yan Li (Advisor)
Betul Hatipoglu (Committee Member)
Anthony Wynshaw-Boris (Committee Member)
Drew Adams (Committee Chair)
122 p.
Biomedical Research; Genetics
genomics, single-cell RNA sequencing, single-cell atac-seq, pancreas, diabetes, beta cell

Recommended Citations

Citations

  • Gu, A. (2023). SINGLE-CELL GENOMICS IDENTIFIES DIABETES-RELEVANT GENES IN HUMAN PANCREATIC ISLETS [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1691008840252809

    APA Style (7th edition)

  • Gu, Anniya. SINGLE-CELL GENOMICS IDENTIFIES DIABETES-RELEVANT GENES IN HUMAN PANCREATIC ISLETS. 2023. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1691008840252809.

    MLA Style (8th edition)

  • Gu, Anniya. "SINGLE-CELL GENOMICS IDENTIFIES DIABETES-RELEVANT GENES IN HUMAN PANCREATIC ISLETS." Doctoral dissertation, Case Western Reserve University, 2023. http://rave.ohiolink.edu/etdc/view?acc_num=case1691008840252809

    Chicago Manual of Style (17th edition)

case1691008840252809
© 2023, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.
Release 3.2.12