Prioritization of ligands and receptors in human islets and stem cell-derived cells
department or school: Science, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Kamal, Sepehr
issued: 2023-04-19T17:32:26Z
issued: 2023
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Diabetes is caused by the dysfunction and/or destruction of insulin-producing pancreatic β-cells, and curative therapy will require their repair, regeneration, or replacement. Beyond insulin, islets have been reported to contain transcripts for hundreds of other ligands and receptors. Some of these intercellular signals may have therapeutic benefit in diabetes, or in efforts to generate insulin-producing cells from stem cells. Over 90% of the small molecules and proteins used to generate stem cell-derived β-like cells (SCβ-cells) are activators or inhibitors of receptors, and modulation of signaling pathways can alter SCβ-cell differentiation. In this study, we systematically mapped intercellular signaling in human islets and stem cell-derived cells, and built prioritized lists of protein ligands and receptors to guide future screening studies. First, we created a custom ligand-receptor database of 422 protein ligands, 349 receptors, and 1552 interactions. We then integrated multiple datasets to rank ligands and receptors in stem cell-derived cells based on gene expression, protein abundance, and differential expression and abundance compared to human islets. We combined the ligand and receptor ranks to rank each interacting ligand-receptor pair. Finally, we presented three prioritized lists to guide future screens: scarce ligands with abundant receptors in stem cell-derived cells, scarce receptors with abundant ligands in stem cell-derived cells, and abundant receptors with abundant ligands in stem cell-derived cells. Collectively, we expect these data will enable future studies to define the roles of ligands and receptors in diabetes and diabetes therapies.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/84326
note: PRIORITIZATION OF LIGANDS AND RECEPTORS IN HUMAN ISLETS AND STEM CELL-DERIVED CELLS by Sepehr Kamal B.Sc., The University of British Columbia, 2017 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Genome Science and Technology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) April 2023 © Sepehr Kamal, 2023 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the thesis entitled: PRIORITIZATION OF LIGANDS AND RECEPTORS IN HUMAN ISLETS AND STEM CELL-DERIVED CELLS submitted by Sepehr Kamal in partial fulfilment of the requirements for the degree of Master of Science in Genome Science and Technology Examining Committee: Dr. James D. Johnson, Professor, Cellular & Physiological Sciences, UBC Supervisor Dr. Francis C. Lynn, Associate Professor, Surgery, UBC Supervisory Committee Member Dr. Wyeth Wasserman, Professor, Medical Genetics, UBC Supervisory Committee Member iii Abstract Diabetes is caused by the dysfunction and/or destruction of insulin-producing pancreatic β-cells, and curative therapy will require their repair, regeneration, or replacement. Beyond insulin, islets have been reported to contain transcripts for hundreds of other ligands and receptors. Some of these intercellular signals may have therapeutic benefit in diabetes, or in efforts to generate insulin-producing cells from stem cells. Over 90% of the small molecules and proteins used to generate stem cell-derived β-like cells (SCβ-cells) are activators or inhibitors of receptors, and modulation of signaling pathways can alter SCβ-cell differentiation. In this study, we systematically mapped intercellular signaling in human islets and stem cell-derived cells, and built prioritized lists of protein ligands and receptors to guide future screening studies. First, we created a custom ligand-receptor database of 422 protein l…
has type: Thesis/Dissertation
date issued: 2023-05
is shown at: 10.14288/1.0431183
language: eng
degree discipline: Genome Science and Technology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Johnson, James D.
type: Text
identifier URI: http://hdl.handle.net/2429/84326