Bovine Formative Embryonic Stem Cell Plasticity in Embryonic and Extraembryonic Differentiation [scRNA-seq]

Bovine embryonic stem cells (bESCs) can greatly enhance understanding of bovine embryonic development and applications for disease-resistance, biomedical and zoonotic pre-clinical models. However, formative bESCs with distinct morphology and complete differentiation capacity are still unreported. We document here the generation of bESCs which are pluripotent both in vitro and in vivo, and efficiently converted into neural progenitor cells (NPCs) and primordial germ cell-like cells (PGCLCs) by direct differentiation. These cells exhibited distinct metabolic features from human and mouse ESCs and early embryos. Formative bESCs contributed to a wide range of cell types within embryonic and extraembryonic tissues after aggregating with mouse and bovine embryos. The establishment of bovine formative ESCs with dual developmental plasticity represents a milestone for agricultural biotechnology and decoding the underlying mechanism of bona fide bovine pluripotency. Overall design: scRNA seq data of D25 bESC-incorporated bovine chimeric embryos.

牛胚胎干细胞（bovine embryonic stem cells，bESCs）可极大拓展人们对牛胚胎发育的认知，并推动其在抗病生物医学、人畜共患病临床前模型领域的应用。然而，具备独特形态与完整分化潜能的定型态牛胚胎干细胞此前尚未见报道。本文报道了可在体外与体内均表现出多能性的牛胚胎干细胞，其可通过直接分化途径高效诱导为神经前体细胞（neural progenitor cells，NPCs）与原始生殖细胞样细胞（primordial germ cell-like cells，PGCLCs）。该类细胞的代谢特征与人类、小鼠胚胎干细胞及早期胚胎存在显著差异。将其与小鼠、牛胚胎聚合后，此类细胞可参与胚胎及胚外组织中多种细胞类型的形成。具备双重发育可塑性的牛定型态胚胎干细胞的建立，为农业生物技术领域以及解析真正意义上的牛多能性内在调控机制树立了重要里程碑。总体实验设计：整合D25期牛胚胎干细胞的牛嵌合胚胎的单细胞RNA测序（single-cell RNA sequencing，scRNA-seq）数据。