Smed-hippo(RNAi) RNA-Seq. Schmidtea mediterranea

The Hippo pathway plays a key role in regulating cell turnover in adult tissues, and abnormalities are consistently associated with human cancers. Initially related with the control of cell proliferation and death, hippo inhibition is commonly linked to an expansion of stem cells and progenitors, which leads to larger organs and tumors. To understand the mechanism through which Hippo directs cell renewal and promotes stemness, we studied its function in planarians, a stem cell-based organism that allows analysis of the complex cellular events underlying tissue renewal in the whole organism. We show that hippo inhibition in planarians decreases cell death, produces cell cycle arrest, and promotes the dedifferentiation of post-mitotic cells. Thus, hippo (RNAi) planarians have extensive undifferentiated areas and overgrowths with no effects on size or cell number. We propose an essential role for hippo in restricting cell plasticity and ensuring genomic stability, and thus in preventing tumoral transformation. Overall design: Transcriptomic analysis on Smed-hippo(RNAi) animals after one, three and four weeks of inhibition. Three replicates were generated per condition from pools of animals.