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| Status |
Public on Aug 11, 2022 |
| Title |
The Hippo pathway links adipocyte plasticity to adipose tissue fibrosis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Fibrosis disrupts adipose tissue (AT) homeostasis in response to chronic caloric excess, exacerbating metabolic dysfunction. The molecular mechanisms linking adipocyte plasticity to AT fibrosis are largely unknown. Here we show that the Hippo pathway is coupled with TGFbeta signaling to orchestrate a functional adipocyte-to-myofibroblast transition in AT fibrosis. We found that Lats1/2-knockout adipocytes could dedifferentiate into DPP4+ progenitor cells and convert to DPP4- myofibroblasts upon TGFbeta stimulation. Macrophages recruited by CCL2 served as a major cell source of TGFbeta. YAP and TAZ, the Hippo downstream effectors, enhanced SMAD2 stability to promote fibrotic responses. Importantly, inhibition of YAP/TAZ activity in obese mice markedly relieved AT fibrosis and improved metabolic homeostasis. Together, our findings identify the Hippo pathway as a molecular switch in the initiation and development of AT fibrosis, implying it as a therapeutic target.
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| Overall design |
RNA sequencing of adipocytes from the constitutive Lats1/2 adipocyte knockout mouse model (Lats1f/fLats2f/fAdipoqCre) and control littermates ((Lats1f/fLats2f/f). Adipocytes isolated from subcutaneous white adipose tissue of four P7 male mice were pooled as a sample.
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| Contributor(s) |
Shen H, Huang X, Zhao Y, Qiu Y |
| Citation(s) |
36229481 |
| |
| Submission date |
Sep 27, 2021 |
| Last update date |
Oct 28, 2022 |
| Contact name |
Hongyu Shen |
| E-mail(s) |
[email protected]
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| Organization name |
Peking University
|
| Street address |
Wang Kezhen Building, No.5 Yiheyuan Road
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| City |
Beijing |
| ZIP/Postal code |
100871 |
| Country |
China |
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| Platforms (1) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA766611 |
| SRA |
SRP338862 |
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