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Status |
Public on Jan 24, 2024 |
Title |
Signaling modality within gp130 receptor enhances tissue regeneration (Canine scRNA-seq) |
Organism |
Canis lupus familiaris |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Adult mammals are incapable of multi-tissue regeneration and augmentation of this potential may drastically shift current therapeutic paradigms. Here, we found that a common co-receptor of IL-6 cytokines, glycoprotein 130 (gp130), serves as a major nexus integrating various context-specific signaling inputs to either promote regenerative outcomes or aggravate disease progression. Via genetic and pharmacological experiments in vitro and in vivo, we demonstrated that a signaling tyrosine 814 (Y814) within gp130 serves as a major cellular stress sensor. Mice with constitutively inactivated Y814 (F814) exhibit regenerative, not reparative, responses after wounding in skin and anti-degenerative responses in the synovial joint. In addition, pharmacological inhibition of gp130 Y814 results in regeneration of multiple tissues in several species as well as disease modification in animal models of osteoarthritis. Our study characterizes a novel molecular mechanism that, if selectively manipulated, enhances the intrinsic regenerative capacity while preventing pathological outcomes in injury and disease.
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Overall design |
Single-cell mRNA sequencing for dog synovium treated with or without R805 using 10x Genomics.
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Contributor(s) |
Evseenko D, Van Handel B |
Citation(s) |
36947594 |
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Submission date |
Mar 05, 2021 |
Last update date |
Jan 25, 2024 |
Contact name |
Denis Evseenko |
E-mail(s) |
evseenko@usc.edu
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Phone |
323-219-0234
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Organization name |
University of Southern California
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Department |
Orthopaedic Surgery
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Lab |
Evseenko Lab
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Street address |
1450 Biggy St
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City |
Los Angeles |
State/province |
CA |
ZIP/Postal code |
90033 |
Country |
USA |
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Platforms (1) |
GPL25760 |
Illumina NovaSeq 6000 (Canis lupus familiaris) |
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Samples (2) |
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This SubSeries is part of SuperSeries: |
GSE168395 |
Signaling modality within gp130 receptor enhances tissue regeneration |
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Relations |
BioProject |
PRJNA706952 |
SRA |
SRP309464 |