Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, 100084 Beijing, China.
Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China.
Stem Cell Reports. 2021 May 11;16(5):1331-1346. doi: 10.1016/j.stemcr.2021.03.018. Epub 2021 Apr 22.
Stem cell-based embryo models by cultured pluripotent and extra-embryonic lineage stem cells are novel platforms to model early postimplantation development. We showed that induced pluripotent stem cells (iPSCs) could form ITS (iPSCs and trophectoderm stem cells) and ITX (iPSCs, trophectoderm stem cells, and XEN cells) embryos, resembling the early gastrula embryo developed in vivo. To facilitate the efficient and unbiased analysis of the stem cell-based embryo model, we set up a machine learning workflow to extract multi-dimensional features and perform quantification of ITS embryos using 3D images collected from a high-content screening system. We found that different PSC lines differ in their ability to form embryo-like structures. Through high-content screening of small molecules and cytokines, we identified that BMP4 best promoted the morphogenesis of the ITS embryo. Our study established an innovative strategy to analyze stem cell-based embryo models and uncovered new roles of BMP4 in stem cell-based embryo models.
基于干细胞的胚胎模型由培养的多能性和胚胎外谱系干细胞组成，是模拟早期着床后发育的新型平台。我们表明诱导多能干细胞（iPSCs）可以形成 ITS（iPSCs 和滋养外胚层干细胞）和 ITX（iPSCs、滋养外胚层干细胞和 XEN 细胞）胚胎，类似于体内发育的早期原肠胚。为了促进基于干细胞的胚胎模型的高效和无偏分析，我们建立了一个机器学习工作流程，使用高内涵筛选系统收集的 3D 图像提取多维特征并对 ITS 胚胎进行定量分析。我们发现不同的 PSC 系在形成类胚胎结构的能力上存在差异。通过对小分子和细胞因子的高内涵筛选，我们发现 BMP4 最能促进 ITS 胚胎的形态发生。我们的研究建立了一种分析基于干细胞的胚胎模型的创新策略，并揭示了 BMP4 在基于干细胞的胚胎模型中的新作用。
