GSE126069
Usp22 controls multiple signaling pathways that are essential for vasculature formation in the mouse placenta
Usp22, a component of the SAGA complex, is over expressed in highly aggressive cancers, but the normal functions of this deubiquitinase are not well defined.  We determined that loss of Usp22 in mice results in embryonic lethality due to defects in extra-embryonic placental tissues and failure to establish proper vascular interactions with the maternal circulatory system.  These phenotypes arise from abnormal gene expression patterns that reflect defective kinase signaling, including TGFß and several receptor tyrosine kinase (RTK) pathways. Usp22 deletion in endothelial cells and pericytes induced from embryonic stem cells also hinders these signaling cascades with detrimental effects on cell survival and differentiation as well as ability to form vessels.  Our findings provide new insights to Usp22 functions during development that may offer clues to its role in disease states. Overall design: To determine changes in gene expression profile upon Usp22 loss in the developing placenta, RNA from day E9.5 placentas from wild-type and Ups22-/- mice s was isolated for deep sequencing, in triplicates and duplicates respectively. Key genes identified from RNAseq were validated by qRT-PCR using RNA from the same samples that were used for sequencing.