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| Status |
Public on Jun 01, 2019 |
| Title |
Linking YAP to Müller glia quiescence exit in the degenerative retina |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Contrasting with fish or amphibian, retinal regeneration from Müller glial cells is largely limited in mammals. In our quest towards the identification of molecular cues that may boost their stemness potential, we investigated the involvement of the Hippo pathway effector YAP, which we previously found to be upregulated in Müller cells following retinal injury. We report that conditional Yap deletion in Müller cells prevents the upregulation of cell cycle genes that normally accompanies reactive gliosis upon photoreceptor cell death. This occurs as a consequence of defective EGFR signaling. Consistent with a function of YAP in triggering Müller glia cell cycle re-entry, we further show that in Xenopus, a species endowed with efficient regenerative capacity, YAP is required for their injury-dependent proliferative response. Finally, and noteworthy, we reveal that YAP overactivation in mouse Müller cells is sufficient to induce their reprogramming into highly proliferative cells. Overall, we unravel a pivotal role for YAP in tuning Müller cell response to injury and highlight a novel YAP-EGFR axis by which Müller cells exit their quiescence state, a critical step towards regeneration.
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| Overall design |
Retinal samples were harvested from Yapflox/flox; Rax-CreERT2 mouse line allowing for Cre-mediated conditional gene ablation specifically in Müller cells. It is named Yap CKO while “control” refers to Yapflox/flox mice. Yap deletion was induced in fully differentiated Müller cells, through 4-hydroxytamoxifen (4-OHT) intraperitoneal injection at P10. All animals were injected with 4-OHT. Each sample included 1 frozen retina and experiments were performed in triplicate. RNA-seq transcriptome libraries were constructed from 1 ug of total RNA.
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| Contributor(s) |
Hamon A, Ail D, García-García D, Bitard J, Dalkara D, Locker M, Roger JE, Perron M |
| Citation(s) |
31067458 |
| |
| Submission date |
Oct 26, 2018 |
| Last update date |
Sep 02, 2019 |
| Contact name |
Jerome Eric Roger |
| E-mail(s) |
jeromeeroger@gmail.com
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| Phone |
+33169156835
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| Organization name |
CNRS-Universite Paris Sud
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| Department |
CERTO
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| Lab |
Neuro-PSI
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| Street address |
151 Route de la Rotonde, Campus CEA Saclay - Bat 151
|
| City |
Saclay |
| State/province |
Please select |
| ZIP/Postal code |
91400 |
| Country |
France |
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| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA498663 |
| SRA |
SRP166961 |
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