Zhu, Hanrui (2024) Cell-cell communication and competition in human pluripotent stem cells. Masters thesis, Memorial University of Newfoundland.
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Abstract
Nearly all of the cells in our body communicate with each other to support tissue and organ function. This cell-cell communication can result in either Co-operation or competition, where fitter cells outcompete less fit cells for space and nutrients. Cell competition has been widely studied during tumorigenesis and cancer metastasis, however less is known about how other cell types compete with each other. Human stem cells have great therapeutic potential for a variety of conditions including heart disease, burns, neurodegenerative disorders and others. Here we investigate whether gap junctional intercellular communication (GJIC) contributes to cell competition in human induced pluripotent stem cells (hiPSCs). Because GJIC has previously been shown to spread pro-apoptotic stimuli, we hypothesize that GJIC-deficient hiPSCs will exhibit enhanced fitness and outcompete GJIC-competent cells. To create GJIC-deficient cells, we used CRISPR-Cas9 to knockout Cx43, which is the main gap junctional protein present in hiPSCs. Immunofluorescence confocal microscopy revealed that Cx43-deficient cells can physically interact with wild type cells and undergo apoptosis at similar rates. Co-culturing resulted in similar proportions of GJIC-competent and deficient cells, as measured by flow cytometry. In conclusion, our results demonstrate that hiPSC cell competition is independent of the gap junction protein, Cx43. Ongoing experiments are evaluating how other Cx isoforms may contribute to hiPSC competition. Understanding how stem cells compete with each other will aid researchers in designing and optimizing safe, effective stem cell therapies for use in regenerative medicine.
| Item Type: | Thesis (Masters) |
|---|---|
| URI: | http://research.library.mun.ca/id/eprint/16587 |
| Item ID: | 16587 |
| Additional Information: | Includes bibliographical references (pages 93-114) -- Restricted until September 30, 2025 |
| Keywords: | stem cell, competition, gap junction intercellular communication, Cx43 |
| Department(s): | Medicine, Faculty of > Biomedical Sciences |
| Date: | October 2024 |
| Date Type: | Submission |
| Medical Subject Heading: | Cell Communication; Cell Competition; Connexin 43; CRISPR-Cas Systems; Regenerative Medicine; Apoptosis; Induced Pluripotent Stem Cells |
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