Southwest Hospital/Southwest Eye Hospital, Army Medical University, Chongqing, China.
Laboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing, China.
IUBMB Life. 2021 Dec;73(12):1432-1445. doi: 10.1002/iub.2571. Epub 2021 Nov 12.
Hippo signaling pathway is involved in many biological processes including the fate decision of embryonic stem cells (ESCs). Yes-associated protein (Yap) function as a key effector of Hippo pathway, but its role in ESCs is still controversial. So far, only two isoforms of Yap have been identified and they have both overlapping and distinct functions. Here, we identify six novel isoforms of mouse Yap, bringing the total number of isoforms to eight. According to the differences in the first exon, they are divided into two subtypes (a and b). Isoform-a and isoform-b exhibit different subcellular localizations. Moreover, isoform-a can fully reverse the impaired self-renewal phenotype induced by Yap knockout (KO). Upon overexpression, isoform-a moderately promotes mESCs self-renewal and markedly delays differentiation. On the contrary, no significant pro-self-renewal phenotype is observed when isoform-b overexpressed in wildtype (WT) mESCs or re-expressed in Yap KO cell lines. These finding not only help to clarify the role of Yap in mESCs, but also lay the foundation for advancing functional researches of Yap in other processes.
Hippo 信号通路参与许多生物学过程，包括胚胎干细胞 (ESCs) 的命运决定。Yes 相关蛋白 (Yap) 作为 Hippo 通路的关键效应物发挥作用，但它在 ESCs 中的作用仍存在争议。到目前为止，已经鉴定出两种 Yap 的同工型，它们具有重叠和不同的功能。在这里，我们鉴定了 6 种新型的小鼠 Yap 同工型，使同工型的总数达到 8 种。根据第一外显子的差异，它们分为两种亚型 (a 和 b)。同工型-a 和同工型-b 表现出不同的亚细胞定位。此外，同工型-a 可以完全逆转 Yap 敲除 (KO) 引起的自我更新表型受损。过表达时，同工型-a 适度促进 mESCs 的自我更新，显著延缓分化。相反，当同工型-b 在野生型 (WT) mESCs 中过表达或在 yap KO 细胞系中重新表达时，没有观察到明显的促进自我更新表型。这些发现不仅有助于阐明 Yap 在 mESCs 中的作用，也为推进 yap 在其他过程中的功能研究奠定了基础。
