Pluto Bioinformatics

GSE94534: Retinal degeneration triggers the activation of YAP/TEAD in reactive Mller cells

Bulk RNA sequencing

PURPOSE. During retinal degeneration, Mller glia cells respond to photoreceptor loss by undergoing reactive gliosis, with both detrimental and beneficial effects. Increasing our knowledge of the complex molecular response of Mller cells to retinal degeneration is thus essential for the development of new therapeutic strategies. The purpose of this work was to identify new factors involved in Mller cell response to photoreceptor cell death. METHODS. Whole transcriptome sequencing was performed from wild-type and degenerating rd10 mouse retinas at P30. The changes in mRNA abundance for several deregulated genes were assessed by RT-qPCR. Protein expression level and retinal cellular localization were determined by western-blot and immunohistochemistry, respectively. RESULTS. Pathway-level analysis from whole transcriptomic data revealed the Hippo/YAP pathway as one of the main signaling pathways altered in response to photoreceptor degeneration in rd10 retinas. We found that downstream effectors of this pathway, YAP and TEAD1, are specifically expressed in Mller cells and that their expression, at both the mRNA and protein levels, is increased in rd10 reactive Mller glia after the onset of photoreceptor degeneration. The expression of Ctgf and Cyr61, two target genes of the transcriptional YAP/TEAD complex, is also upregulated following photoreceptor loss. CONCLUSIONS. This work reveals for the first time that YAP and TEAD1, key downstream effectors of the Hippo pathway, are specifically expressed in Mller cells. We also uncovered a deregulation of the expression and activity of Hippo/YAP pathway components in reactive Mller cells under pathological conditions. SOURCE: Jerome,Eric,Roger (jeromeeroger@gmail.com) - Neuro-PSI CNRS-Universite Paris Sud