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Gastrulation establishes the three primary tissues of an embryo: the ectoderm, mesoderm, and endoderm. This developmental process relies on a series of intricate cellular movements, which in humans transforms a flat, “bilaminar disc” composed of two cell sheets into a three-tiered structure. In the resulting embryo, the endoderm serves as the bottom layer, and stacked directly above it is the intermediate mesoderm, and then the uppermost ectoderm. Respectively, these tissue strata...
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Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
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Modeling post-gastrula development via bidirectional pluripotent stem cells.

Kuisheng Liu1,2, Zihui Yan1,2, Dandan Bai1,2

  • 1Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.

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|August 29, 2025
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Summary
This summary is machine-generated.

Scientists developed a new medium to create bidirectional pluripotent stem cells (BPSCs). These cells efficiently generate multiple embryonic lineages, aiding in studying early development and creating advanced embryo models.

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Genetics

Background:

  • Recapitulating early embryonic development is challenging due to the lack of stem cells that can efficiently generate both trophoblast and epiblast lineages.
  • Existing methods struggle to precisely mimic the initial stages of embryonic differentiation.

Purpose of the Study:

  • To establish a novel method for generating stem cells capable of efficient bidirectional differentiation.
  • To investigate the potential of these cells in modeling early embryonic development and human cell differentiation.

Main Methods:

  • High-content chemical screening to identify optimal culture conditions.
  • Establishment of an AL medium for generating mouse bidirectional pluripotent stem cells (BPSCs).
  • In vitro and in vivo differentiation assays, Wnt signaling pathway analysis, and generation of E8.5 embryo models.

Main Results:

  • Mouse BPSCs co-expressing OCT4 and CDX2 were generated, exhibiting high plasticity for trophoblast, epiblast, and primitive endoderm differentiation within 48 hours.
  • BPSCs contributed efficiently to embryonic and extraembryonic tissues in vivo.
  • Wnt signaling hyperactivation via a Lef1-dependent bypass was identified as a key mechanism.
  • Integration with a primitive endoderm induction system enabled high-efficiency generation of E8.5 embryo models that recapitulated key developmental milestones.
  • Human cells cultured under AL conditions showed conserved OCT4 and CDX2 double-positive states.

Conclusions:

  • Bidirectional pluripotent stem cells (BPSCs) represent a significant advancement for studying early lineage specification.
  • The developed culturing platform is effective across species, offering a powerful tool for developmental biology research.
  • Advanced embryo models generated using BPSCs facilitate the study of post-gastrulation development and morphogenesis.