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Related Concept Videos

Induced Pluripotent Stem Cells01:13

Induced Pluripotent Stem Cells

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 called induced pluripotent stem...

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In Vitro Differentiation of Human Pluripotent Stem Cells into Trophoblastic Cells
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Naive pluripotent stem cell-based models capture FGF-dependent human hypoblast lineage specification.

Anish Dattani1, Elena Corujo-Simon2, Arthur Radley3

  • 1Living Systems Institute, University of Exeter, Exeter, UK; Department of Clinical & Biomedical Sciences, University of Exeter Medical School, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.

Cell Stem Cell
|June 1, 2024
PubMed
Summary

Human naive pluripotent stem cells (PSCs) differentiate into hypoblast via a transitional inner cell mass-like state. Fibroblast growth factor (FGF) signaling is crucial for this early human embryogenesis process.

Keywords:
FGFblastocystcell fateembryo modelhuman naive pluripotent stem cellshypoblast

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Human Embryogenesis

Background:

  • The hypoblast is a critical extraembryonic tissue originating from the blastocyst's inner cell mass.
  • Studying human embryogenesis is challenging, necessitating reliable stem cell models.
  • Human naive pluripotent stem cells (PSCs) offer a valuable model for investigating early developmental events.

Purpose of the Study:

  • To elucidate the differentiation pathway of human naive PSCs into hypoblast.
  • To identify key signaling pathways regulating hypoblast specification in vitro and in vivo.
  • To establish conservation in lineage specification between human and mouse embryos.

Main Methods:

  • Utilized human naive PSCs to model hypoblast differentiation.
  • Investigated the role of fibroblast growth factor (FGF) signaling during differentiation.
  • Manipulated signaling pathways to enhance hypoblast induction while limiting trophectoderm and epiblast fates.

Main Results:

  • Human naive PSC differentiation to hypoblast involves a transitional inner cell mass-like state.
  • A specific window of fibroblast growth factor (FGF) signaling is critical for hypoblast specification.
  • Inhibition of FGF signaling in early human blastocysts impairs hypoblast formation.
  • In vitro hypoblast induction is enhanced by concurrently limiting trophectoderm and epiblast differentiation.

Conclusions:

  • Human naive PSCs recapitulate in vivo hypoblast differentiation trajectories.
  • Fibroblast growth factor (FGF) signaling plays a conserved, critical role in human hypoblast formation.
  • This study refines understanding of early lineage specification and highlights the utility of PSC models for human embryogenesis research.