Transcription coactivator YAP1 promotes CCND1/CDK6 expression,stimulating cell proliferation in cloned cattle placentas  

作　　者：Shan-Shan Wu Xiao-Yu Zhao Lei Yang Chao Hai Di Wu Xue-Fei Liu Li-Shuang Song Chun-Ling Bai Guang-Hua Su Guang-Peng Li 

机构地区：[1]State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock(R2BGL),Inner Mongolia University,Hohhot,Inner Mongolia 010070,China [2]College of Life Sciences,Inner Mongolia University,Hohhot,Inner Mongolia 010070,China

出　　处：《Zoological Research》2025年第1期122-138,共17页动物学研究(英文)

基　　金：supported by the National Natural Science Foundation of China (32060755);Natural Science Foundation of Inner Mongolia (2024MS03001);Inner Mongolia Autonomous Region Open Competition Projects (2022JBGS0018);Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region (NJYT23090);Inner Mongolia Autonomous Region Science and Technology Leading Team (2022LJRC0006);Inner Mongolia Autonomous Region Science and Technology Major Project (2021ZD0009);Major Agricultural Science and Technology Project of the Ministry of Agriculture and Rural Affairs (NK2022130203);Central Government Guides Local Science and Technology Development Funds (2022ZY0212);Inner Mongolia Autonomous Region High-level Talent Support Program;Inner Mongolia University Chief Scientist Program。

摘　　要：Somatic cell nuclear transfer(SCNT)has been successfully employed across various mammalian species,yet cloned animals consistently exhibit low pregnancy rates,primarily due to placental abnormalities such as hyperplasia and hypertrophy.This study investigated the involvement of the Hippo signaling pathway in aberrant placentaldevelopmentinSCNT-inducedbovine pregnancies.SCNT-derived cattle exhibited placental hypertrophy,including enlarged abdominal circumference and altered placental cotyledon morphology.RNA sequencing analysis indicated significant dysregulation of Hippo signaling pathway genes in SCNT placentas.Coexpression of YAP1 and CCND1 was observed in cloned blastocysts,placental tissues,and bovine placental mesenchymal stem cells(bPMSCs).Manipulation of YAP1expression demonstrated the capacity to regulate bPMSC proliferation.Experimental assays confirmed the direct binding of YAP1 to CCND1,which subsequently promoted CCND1 expression in bPMSCs.Furthermore,inhibition of CDK6,a downstream target of CCND1,attenuated SCNT bPMSC proliferation.This study identified YAP1 as a key regulatory component within the Hippo signaling pathway that drives placental hyperplasia in cloned cattle through up-regulation of CCND1-CDK6 expression,facilitating cell cycle progression.These findings offer potential avenues for enhancing cloning efficiency,with implications for evolutionary biology and the conservation of valuable germplasm resources.

关 键 词：Somatic cell nuclear transfer Cloned cattle Placental hypertrophy Cell proliferation CCND1-CDK6 YAP1 

分 类 号：Q813[生物学—生物工程]