Transcription coactivator YAP1 promotes CCND1/CDK6 expression, stimulating cell proliferation in cloned cattle placentas
Year: 2024
Type: article
Abstract: 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 placental development in SCNT-induced bovine 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. Co-expression of YAP1 and CCND1 was observed in cloned blastocysts, placental tissues, and bovine placental mesenchymal stem cells (bPMSCs). Manipulation of YAP1 expression 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.
Source: 动物学研究
Authors: Wu Shan-Shan, 内蒙古大学草原家畜生殖调控与繁育国家重点实验室(R2BGL), 内蒙古 呼和浩特 010070, 中国, Zhao Xiao-Yu, Yang Lei, Hai Chao, Wu Di, Liu Xue-Fei, Song Li-Shuang, Bai Chun-Ling, Su Guang-Hua, Li Guang-Peng, 内蒙古大学生命科学学院, 内蒙古 呼和浩特 010070, 中国
Institution: Inner Mongolia University
Language: English
Subfield: Cell Biology
Domain: Life Sciences
SDG: Zero hunger
Open Access status: diamond
OpenAlex ID: W4403683655