Laboratory of Molecular Diagnostics and Cell Biology, College of Veterinary Medicine, Gyeongsang National University, Jinju, 52828, Republic of Korea.
Laboratory of Veterinary Embryology and Biotechnology, Veterinary Medical Center, College of Veterinary Medicine, Chungbuk National University, Cheongju, 28644, Republic of Korea.
Biol Res. 2024 May 30;57(1):35. doi: 10.1186/s40659-024-00516-y.
Genetically modified pigs are considered ideal models for studying human diseases and potential sources for xenotransplantation research. However, the somatic cell nuclear transfer (SCNT) technique utilized to generate these cloned pig models has low efficiency, and fetal development is limited due to placental abnormalities.
In this study, we unprecedentedly established putative porcine trophoblast stem cells (TSCs) using SCNT and in vitro-fertilized (IVF) blastocysts through the activation of Wing-less/Integrated (Wnt) and epidermal growth factor (EGF) pathways, inhibition of transforming growth factor-β (TGFβ) and Rho-associated protein kinase (ROCK) pathways, and supplementation with ascorbic acid. We also compared the transcripts of putative TSCs originating from SCNT and IVF embryos and their differentiated lineages. A total of 19 porcine TSCs exhibiting typical characteristics were established from SCNT and IVF blastocysts (TSCs and TSCs). Compared with the TSCs, TSCs showed distinct expression patterns suggesting unique TSCs characteristics, including decreased mRNA expression of genes related to apposition, steroid hormone biosynthesis, angiopoiesis, and RNA stability.
This study provides valuable information and a powerful model for studying the abnormal development and dysfunction of trophoblasts and placentas in cloned pigs.
基因修饰猪被认为是研究人类疾病的理想模型,也是异种移植研究的潜在来源。然而,用于生成这些克隆猪模型的体细胞核移植(SCNT)技术效率较低,由于胎盘异常,胎儿发育受到限制。
在这项研究中,我们通过激活 Wnt/整合(Wnt)和表皮生长因子(EGF)途径、抑制转化生长因子-β(TGFβ)和 Rho 相关蛋白激酶(ROCK)途径以及补充抗坏血酸,以前所未有的方式从 SCNT 和体外受精(IVF)囊胚中建立了假定的猪滋养层干细胞(TSC)。我们还比较了源自 SCNT 和 IVF 胚胎的假定 TSCs 及其分化谱系的转录本。总共从 SCNT 和 IVF 囊胚中建立了 19 株具有典型特征的猪 TSC(TSC 和 TSC)。与 TSC 相比,TSC 表现出独特的表达模式,表明其具有独特的 TSC 特征,包括与贴附、甾体激素生物合成、血管生成和 RNA 稳定性相关的基因的 mRNA 表达降低。
这项研究为研究克隆猪中滋养层和胎盘的异常发育和功能障碍提供了有价值的信息和强大的模型。