Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Vaud, 1015, Lausanne, Switzerland.
Roche Institute for Translational Bioengineering (ITB), Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
Sci Rep. 2022 Aug 4;12(1):13380. doi: 10.1038/s41598-022-17265-1.
Gastruloids are three-dimensional embryonic organoids that reproduce key features of early mammalian development in vitro with unique scalability, accessibility, and spatiotemporal similarity to real embryos. Recently, we adapted the gastruloid culture conditions to promote cardiovascular development. In this work, we extended these conditions to capture features of embryonic blood development through a combination of immunophenotyping, detailed transcriptomics analysis, and identification of blood stem/progenitor cell potency. We uncovered the emergence of blood progenitor and erythroid-like cell populations in late gastruloids and showed the multipotent clonogenic capacity of these cells, both in vitro and after transplantation into irradiated mice. We also identified the spatial localization near a vessel-like plexus in the anterior portion of gastruloids with similarities to the emergence of blood stem cells in the mouse embryo. These results highlight the potential and applicability of gastruloids to the in vitro study of complex processes in embryonic blood development with spatiotemporal fidelity.
类囊胚是三维胚胎类器官，可在体外重现早期哺乳动物发育的关键特征，具有独特的可扩展性、可及性和与真实胚胎的时空相似性。最近，我们调整了类囊胚培养条件，以促进心血管发育。在这项工作中，我们通过免疫表型分析、详细的转录组学分析以及鉴定血液干/祖细胞的潜能，扩展了这些条件，以捕获胚胎血液发育的特征。我们在晚期类囊胚中发现了造血祖细胞和红细胞样细胞群的出现，并显示了这些细胞的多能克隆形成能力，无论是在体外还是在移植到辐照小鼠后。我们还确定了在类囊胚前部类似于血管样丛的位置的空间定位，与小鼠胚胎中造血干细胞的出现具有相似性。这些结果突出了类囊胚在体外研究胚胎血液发育复杂过程中的潜力和适用性，具有时空保真度。
