Transcription co-activator YAP1 promotes the expression of CCND1/CDK6, stimulating cell proliferation and inducing placental hypertrophy in cloned cattle

Somatic cell nuclear transfer (SCNT) has been successful in various mammalian species, but low pregnancy rates in cloned animals are often linked to placental issues, particularly hyperplasia and hypertrophy.This study investigated the role of the Hippo signaling pathway in abnormal SCNT bovine placentas. SCNT cattle exhibited placental hypertrophy, including prolonged gestation, increased abdominal circumference, and altered placental cotyledon features. RNA-seq analysis revealed abnormal expression of Hippo signaling pathway genes in SCNT placentas. YAP1 and CCND1 were co-expressed in cloned blastocysts, placental tissues, and placental mesenchymal stem cells (bPMSCs). Regulating the expression of YAP1 can modulate the proliferation of bPMSCs. Experiments confirmed direct binding of YAP1 to CCND1 and its promotion of CCND1 expression in bPMSCs. Inhibition of CDK6, a downstream target of CCND1, can attenuated the proliferation of SCNT bPMSCs. This study elucidates that YAP1 in the Hippo signaling pathway regulates placental hyperplasia in cloned cattle by promoting the expression of CCND1-CDK6 and cell cycle progression, providing potential avenues for enhancing animal cloning efficiency. This study not only advances cloning technology but also contributes to evolutionary biology and germplasm conservation.