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All forms of plasticity are tightly regulated to ensure proper tissue function, and when aberrantly activated, can contribute to pathological phenotypes, including impaired tissue repair and tumorigenesis. Understanding how cellular identity is dysregulated during aging, injury, and disease may yield approaches that correct aberrant cell fate transitions with therapeutic applications. This dissertation seeks to characterize the factors that guard cell fate by integrating innovative experimental techniques, including novel cell lines, animal models, and micro-engineered devices, with high-throughput sequencing assays and bioinformatics tools that map molecular information to cellular responses.\u00a0\r\n\r\nThe first three studies provide insights into the mechanisms that preserve the regenerative capacity of muscle stem cells (MuSCs), the resident stem cell population in skeletal muscle. MuSCs lie in a state of mitotic quiescence during homeostasis and activate upon injury to repair damaged tissue while also renewing the quiescent stem cell pool. Over time, MuSCs accumulate intracellular damage that alters metabolic signaling pathways and transcriptional programs supportive of quiescence, blunting the efficient regeneration of skeletal muscle. To further understand how MuSCs acquire dysfunctional molecular programs in old age, we explore the roles of three-dimensional genome organization, an underexplored histone modification (H4K20me1), and a conserved metabolic regulator (Sestrins) in mediating pathological gene expression both at rest and in response to injury. We find that natural aging in MuSCs is accompanied by subtle shifts in global genome architecture and metabolic signaling that are sufficient to induce aberrant regenerative trajectories.\u00a0\r\n\r\nThe fourth and fifth studies describe continuing efforts to develop new models for engineering cell fate. In one study, we identify barriers to cell fate transitions by reprogramming somatic cells such that a specialized cell fate is erased and a new identity is adopted. This process requires spatial remodeling of the epigenetic landscape that is constrained by interactions between peripheral heterochromatin and the protein scaffold that lines the interior of the nucleus. We show that manipulating components of the nuclear scaffold prior to reprogramming alters mechanical properties of the nucleus and peripheral heterochromatin organization, which converge to drive changes in reprogramming dynamics. Finally, we revisit a century-old hypothesis that tumor cells acquire enhanced metastatic potential through fusion with neighboring stromal cells that express pro-metastatic traits such as motility, chemotaxis, and tissue tropism. To investigate this concept, we demonstrate the efficient production of bi-species heterokaryons from human tumor cells and mouse stromal cells in the brain metastatic niche, which allows genetic and metabolic factors to be assigned to their parent cell by species identity. This approach will allow us to identify and inhibit trans-acting factors that promote malignant fate transitions.\u00a0\r\n\r\nIn summary, this thesis provides mechanistic insights into cell fate plasticity in varying health contexts and explores new models for deciphering cell fate regulation.\r\n\r\nCommittee Chair(s): Dr. Carlos A. Aguilar\r\n\r\nZoom Link: https:\/\/umich.zoom.us\/meeting\/register\/tJ0td-2oqDorHNTHn8ikj0vDQx7x7ljfl7uy", "occurrence_notes":null, "guid":"102851-21805240@events.umich.edu", "permalink":"http:\/\/events.umich.edu\/event\/102851", "building_id":"null", "building_name":"North Campus Research Complex Building 10", "campus_maps_id":"615", "room":"Research Auditorium", "location_name":"North Campus Research Complex Building 10", "has_livestream":1, "livestream_type":"other", "livetream_require_login":0, "livestream_id":"0280777", "livestream_link":"https:\/\/umich.zoom.us\/meeting\/register\/tJ0td-2oqDorHNTHn8ikj0vDQx7x7ljfl7uy", "cost":"", "tags":["biomedical","biomedical engineering","bme","engineering","Medicine","Michigan Engineering"], "website":"", "sponsors":[ { "group_name":"Biomedical Engineering", "group_id":"1143", "website":"https:\/\/www.facebook.com\/profile.php?id=100094127215673" } ], "image_url":"https:\/\/events.umich.edu\/media\/attachments\/2023\/01\/event_102851_original-1.png", "styled_images":{ "event_thumb":"https:\/\/events.umich.edu\/media\/cache\/event_thumb\/media\/attachments\/2023\/01\/event_102851_original-1.png", "event_large":"https:\/\/events.umich.edu\/media\/cache\/event_large\/media\/attachments\/2023\/01\/event_102851_original-1.png", "event_large_2x":"https:\/\/events.umich.edu\/media\/cache\/event_large_2x\/media\/attachments\/2023\/01\/event_102851_original-1.png", "event_large_lightbox":"https:\/\/events.umich.edu\/media\/cache\/event_large_lightbox\/media\/attachments\/2023\/01\/event_102851_original-1.png", "group_thumb":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_thumb\/media\/attachments\/2023\/01\/event_102851_original-1.png", "group_thumb_square":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_thumb_square\/media\/attachments\/2023\/01\/event_102851_original-1.png", "group_large":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_large\/media\/attachments\/2023\/01\/event_102851_original-1.png", "group_large_lightbox":"https:\/\/events.umich.edu\/media\/cache\/resolve\/group_large_lightbox\/media\/attachments\/2023\/01\/event_102851_original-1.png", "event_large_crop":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_large_crop\/media\/attachments\/2023\/01\/event_102851_original-1.png", "event_list":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_list\/media\/attachments\/2023\/01\/event_102851_original-1.png", "event_list_2x":"https:\/\/events.umich.edu\/media\/cache\/event_list_2x\/media\/attachments\/2023\/01\/event_102851_original-1.png", "event_grid":"https:\/\/events.umich.edu\/media\/cache\/event_grid\/media\/attachments\/2023\/01\/event_102851_original-1.png", "event_grid_2x":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_grid_2x\/media\/attachments\/2023\/01\/event_102851_original-1.png", "event_feature_large":"https:\/\/events.umich.edu\/media\/cache\/event_feature_large\/media\/attachments\/2023\/01\/event_102851_original-1.png", "event_feature_thumb":"https:\/\/events.umich.edu\/media\/cache\/resolve\/event_feature_thumb\/media\/attachments\/2023\/01\/event_102851_original-1.png" }, "occurrence_count":1, "first_occurrence":21805240 } , "96537-21803806": { "datetime_modified":"20221215T162044", "datetime_start":"20230111T121500", "datetime_end":"20230111T124500", "has_end_time":1, "date_start":"2023-01-11", "date_end":"2023-01-11", "time_start":"12:15:00", "time_end":"12:45:00", "time_zone":"America\/Detroit", "event_title":"VIRTUAL | CEW+INSPIRE MIDWEEK MINDFULNESS GUIDED SITS", "occurrence_title":"", "combined_title":"VIRTUAL | CEW+INSPIRE MIDWEEK MINDFULNESS GUIDED SITS", "event_subtitle":"", "event_type":"Well-being", "event_type_id":"12", "description":"RSVP here: https:\/\/umich.zoom.us\/meeting\/register\/tJAqceGoqDosHN15uxUlzCWWN6qwjNjSQpj_ \r\n\r\nJoin us in community to practice mindfulness meditation, a life-enhancing skill that can be learned with consistent practice. This formal, largely-guided, practice utilizes evidence-based cognitive training that bolsters one's ability to handle stress, poor mood, and threat.\u00a0 This weekly mindfulness practice encourages present moment, non-judgemental, awareness \u2013 noticing where your focus and attention are and continually inviting attention to current mind and body sensations in a kind and compassionate way.\r\n\r\nMindfulness meditation opens the possibility to pause, gain perspective, attend to the present, and respond accordingly. In our ever-changing, complex, and challenging world, mindfulness can provide grounding. 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