{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/113950"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/113950","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Myogenic functions of muscle-derived cytokines","abstract":"Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2023-12-01","abstract_html":"Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2023-12-01","abstract_has_math":false,"creators":["Kim, Dongwook"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Cell and Developmental Biology","degree_department":null,"school":null,"contributors":["Chen, Jie","Stubbs, Lisa","Li, Xin","Boppart, Marni"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-04-29T21:42:53Z","date_published":"2022-04-29T21:42:53Z","updated_at":"2026-07-22T22:24:53Z","subjects":["Biology"],"languages":["en","eng"],"rights":["Copyright 2021 Dongwook Kim"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/113950","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Chen, Jie","Stubbs, Lisa","Li, Xin","Boppart, Marni"]},{"key":"dc:creator","label":"Author","values":["Kim, Dongwook"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2022-04-29T21:42:53Z","2024-04-29T21:47:53Z","2021-12","2021-09-14"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Cell and Developmental Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en","eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2021 Dongwook Kim"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/113950"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2023-12-01","The student, Dongwook Kim, accepted the attached license on 2021-09-09 at 10:35.","The student, Dongwook Kim, submitted this Dissertation for approval on 2021-09-09 at 10:44.","This Dissertation was approved for publication on 2021-09-14 at 09:30.","DSpace SAF Submission Ingestion Package generated from Vireo submission #17128 on 2022-04-06 at 17:16:34","Made available in DSpace on 2022-04-29T21:42:53Z (GMT). No. of bitstreams: 3 KIM-DISSERTATION-2021.pdf: 6177591 bytes, checksum: bf61b323910fce261afb38758cc49540 (MD5) LICENSE.txt: 4209 bytes, checksum: 82ae3a4b6f7b945e3f1c2719ce0868c8 (MD5) PROQUEST_LICENSE.txt: 4555 bytes, checksum: cf0de6ef9efa701e9f040dc89c695bfd (MD5) Previous issue date: 2021-09-14","Embargo set by: Seth Robbins for item 123312 Lift date: 2024-04-29T21:43:01Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 123312 Lift date: 2024-04-29T21:44:44Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 123312 Lift date: 2024-04-29T21:46:25Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 123312 Lift date: 2024-04-29T21:47:53Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","U of I Only","Adult skeletal muscle has a robust capacity for regeneration, partially recapitulating the embryonic development process. Upon injury, quiescent muscle stem cells, known as satellite cells, are activated, and they proliferate to produce myoblasts at the injury site. These myoblasts withdraw from the cell cycle and enter the myogenic differentiation process. Differentiated myoblasts further fuse together to form new multi-nucleated myofibers or repair existing ones. Many of the regulators of this highly orchestrated myogenic process are still unknown or incompletely understood. It was long assumed that the immune cells that infiltrate muscle injury sites secrete cytokines that can regulate not only inflammatory responses but also muscle regeneration. However, there have been multiple reports of cytokine secretion by muscle cells, and our lab’s functional screening using RNAi identified numerous cytokines that can potentially regulate myogenic differentiation of C2C12 mouse myoblasts. TNF-related apoptosis-inducing ligand (TRAIL) emerged from our RNAi screen as a potential negative regulator of myogenic differentiation. In Chapter 2, we demonstrate that TRAIL inhibits cell cycle withdrawal, thereby preventing subsequent myogenic differentiation through its cognate receptor, TRAIL-R2. This action is mediated by the ERK signaling pathway. Remarkably, depletion of TRAIL using shRNA delivery enhances in vivo muscle regeneration upon injury. To date, there have been very few studies that directly examine the source of cytokines (i.e., muscle versus immune cells) that can regulate skeletal muscle regeneration in vivo. To address this major gap in the field, we have generated myogenic progenitor cell (MPC)-specific Cas9 knock-in mice as a system to examine the function of muscle-derived cytokines in skeletal muscle regeneration as described in Chapter 3. From two types of Cas9 knock-in transgenic mice, expression of Cas9 is driven by Pax7 and Myf5, respectively. I have validated that Cas9 is predominantly expressed in skeletal muscle in those mice, and intramuscular delivery of an AAV9-packaged sgRNA has led to successful editing of a target gene. Lastly, in Chapter 4, we investigate the function of chemokine (C-C motif) ligand-8 (Ccl8) in skeletal myogenesis. Although it was previously reported that a cocktail of CCR2 ligands (recombinant Ccl2, Ccl7 and Ccl8) inhibited skeletal myogenesis, the endogenous Ccl8’s function had not been investigated. In C2C12 cells, I find knockdown of Ccl8 to enhance myogenic differentiation. Moreover, utilizing the CRISPR mouse system established in Chapter 3, I have depleted Ccl8 specifically in MPCs and observed accelerated injury-induced muscle regeneration, which provides definitive evidence for the role of muscle-derived Ccl8 in vivo. With the MPC-specific Cas9 mouse model successfully established, we are in the position to investigate many putative muscle-derived cytokines in vivo. A comprehensive understanding of these muscle-specific regulators can contribute to therapeutic development such as stem cell therapy to treat muscle diseases."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Myogenic functions of muscle-derived cytokines"]}]}],"canonical_facts":{"dc:contributor":["Chen, Jie","Stubbs, Lisa","Li, Xin","Boppart, Marni"],"dc:creator":["Kim, Dongwook"],"dc:date":["2022-04-29T21:42:53Z","2024-04-29T21:47:53Z","2021-12","2021-09-14"],"dc:description":["Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2023-12-01","The student, Dongwook Kim, accepted the attached license on 2021-09-09 at 10:35.","The student, Dongwook Kim, submitted this Dissertation for approval on 2021-09-09 at 10:44.","This Dissertation was approved for publication on 2021-09-14 at 09:30.","DSpace SAF Submission Ingestion Package generated from Vireo submission #17128 on 2022-04-06 at 17:16:34","Made available in DSpace on 2022-04-29T21:42:53Z (GMT). No. of bitstreams: 3 KIM-DISSERTATION-2021.pdf: 6177591 bytes, checksum: bf61b323910fce261afb38758cc49540 (MD5) LICENSE.txt: 4209 bytes, checksum: 82ae3a4b6f7b945e3f1c2719ce0868c8 (MD5) PROQUEST_LICENSE.txt: 4555 bytes, checksum: cf0de6ef9efa701e9f040dc89c695bfd (MD5) Previous issue date: 2021-09-14","Embargo set by: Seth Robbins for item 123312 Lift date: 2024-04-29T21:43:01Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 123312 Lift date: 2024-04-29T21:44:44Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 123312 Lift date: 2024-04-29T21:46:25Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 123312 Lift date: 2024-04-29T21:47:53Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","U of I Only","Adult skeletal muscle has a robust capacity for regeneration, partially recapitulating the embryonic development process. Upon injury, quiescent muscle stem cells, known as satellite cells, are activated, and they proliferate to produce myoblasts at the injury site. These myoblasts withdraw from the cell cycle and enter the myogenic differentiation process. Differentiated myoblasts further fuse together to form new multi-nucleated myofibers or repair existing ones. Many of the regulators of this highly orchestrated myogenic process are still unknown or incompletely understood. It was long assumed that the immune cells that infiltrate muscle injury sites secrete cytokines that can regulate not only inflammatory responses but also muscle regeneration. However, there have been multiple reports of cytokine secretion by muscle cells, and our lab’s functional screening using RNAi identified numerous cytokines that can potentially regulate myogenic differentiation of C2C12 mouse myoblasts. TNF-related apoptosis-inducing ligand (TRAIL) emerged from our RNAi screen as a potential negative regulator of myogenic differentiation. In Chapter 2, we demonstrate that TRAIL inhibits cell cycle withdrawal, thereby preventing subsequent myogenic differentiation through its cognate receptor, TRAIL-R2. This action is mediated by the ERK signaling pathway. Remarkably, depletion of TRAIL using shRNA delivery enhances in vivo muscle regeneration upon injury. To date, there have been very few studies that directly examine the source of cytokines (i.e., muscle versus immune cells) that can regulate skeletal muscle regeneration in vivo. To address this major gap in the field, we have generated myogenic progenitor cell (MPC)-specific Cas9 knock-in mice as a system to examine the function of muscle-derived cytokines in skeletal muscle regeneration as described in Chapter 3. From two types of Cas9 knock-in transgenic mice, expression of Cas9 is driven by Pax7 and Myf5, respectively. I have validated that Cas9 is predominantly expressed in skeletal muscle in those mice, and intramuscular delivery of an AAV9-packaged sgRNA has led to successful editing of a target gene. Lastly, in Chapter 4, we investigate the function of chemokine (C-C motif) ligand-8 (Ccl8) in skeletal myogenesis. Although it was previously reported that a cocktail of CCR2 ligands (recombinant Ccl2, Ccl7 and Ccl8) inhibited skeletal myogenesis, the endogenous Ccl8’s function had not been investigated. In C2C12 cells, I find knockdown of Ccl8 to enhance myogenic differentiation. Moreover, utilizing the CRISPR mouse system established in Chapter 3, I have depleted Ccl8 specifically in MPCs and observed accelerated injury-induced muscle regeneration, which provides definitive evidence for the role of muscle-derived Ccl8 in vivo. With the MPC-specific Cas9 mouse model successfully established, we are in the position to investigate many putative muscle-derived cytokines in vivo. A comprehensive understanding of these muscle-specific regulators can contribute to therapeutic development such as stem cell therapy to treat muscle diseases."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/2142/113950"],"dc:language":["en","eng"],"dc:rights":["Copyright 2021 Dongwook Kim"],"dc:subject":["Biology"],"dc:title":["Myogenic functions of muscle-derived cytokines"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Cell and Developmental Biology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:24:53Z"}