Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia.
Nature. 2021 Mar;591(7851):627-632. doi: 10.1038/s41586-021-03372-y. Epub 2021 Mar 17.
Human pluripotent and trophoblast stem cells have been essential alternatives to blastocysts for understanding early human development. However, these simple culture systems lack the complexity to adequately model the spatiotemporal cellular and molecular dynamics that occur during early embryonic development. Here we describe the reprogramming of fibroblasts into in vitro three-dimensional models of the human blastocyst, termed iBlastoids. Characterization of iBlastoids shows that they model the overall architecture of blastocysts, presenting an inner cell mass-like structure, with epiblast- and primitive endoderm-like cells, a blastocoel-like cavity and a trophectoderm-like outer layer of cells. Single-cell transcriptomics further confirmed the presence of epiblast-, primitive endoderm-, and trophectoderm-like cells. Moreover, iBlastoids can give rise to pluripotent and trophoblast stem cells and are capable of modelling, in vitro, several aspects of the early stage of implantation. In summary, we have developed a scalable and tractable system to model human blastocyst biology; we envision that this will facilitate the study of early human development and the effects of gene mutations and toxins during early embryogenesis, as well as aiding in the development of new therapies associated with in vitro fertilization.
人类多能干细胞和滋养层干细胞一直是研究早期人类发育的囊胚替代物。然而,这些简单的培养系统缺乏足够的复杂性,无法充分模拟早期胚胎发育过程中的时空细胞和分子动态。在这里,我们描述了将成纤维细胞重编程为体外三维人类囊胚模型,称为 iBlastoids。iBlastoids 的特征表明它们模拟了囊胚的整体结构,呈现出类似于内细胞团的结构,具有上胚层和原始内胚层样细胞、囊胚腔样腔和滋养外胚层样外层细胞。单细胞转录组学进一步证实了上胚层、原始内胚层和滋养外胚层样细胞的存在。此外,iBlastoids 可以产生多能干细胞和滋养层干细胞,并能够在体外模拟着床早期的几个方面。总之,我们已经开发出一种可扩展和易于处理的系统来模拟人类囊胚生物学;我们设想这将有助于研究早期人类发育以及基因突变和毒素在早期胚胎发生过程中的影响,并有助于开发与体外受精相关的新疗法。
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