Machine learning-assisted high-content analysis of pluripotent stem cell-derived embryos in vitro.

Journal: Stem cell reports
PMID: 33891867

Abstract

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.

Authors

  • Jianying Guo
    PingAn Health Technology, Beijing, China.
  • Peizhe Wang
    Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China.
  • Berna Sozen
    Mammalian Embryo and Stem Cell Group, Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK; Department of Genetics, School of Medicine, Yale University, New Haven, CT 06510, USA.
  • Hui Qiu
    Department of Emergency Surgery, The west campus of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Yonglin Zhu
    Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China.
  • Xingwu Zhang
    Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China.
  • Jia Ming
    Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China.
  • Magdalena Zernicka-Goetz
    Mammalian Embryo and Stem Cell Group, Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK; California Institute of Technology, Division of Biological Engineering, 1200 E. California Boulevard, Pasadena, CA 91125, USA. Electronic address: mz205@cam.ac.uk.
  • Jie Na
    Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: jie.na@tsinghua.edu.cn.

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