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Embryonic Stem Cells00:57

Embryonic Stem Cells

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Embryonic stem (ES) cells were first discovered in mice in 1981 by Martin Evans. In 1998, James Thomson identified a method to isolate embryonic stem cells from humans. Human embryonic stem cells (hESCs) are obtained from 3-5 day old embryos that remain unused after an in vitro fertilization procedure.
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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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Updated: Aug 30, 2025

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Modeling human extraembryonic mesoderm cells using naive pluripotent stem cells.

Thi Xuan Ai Pham1, Amitesh Panda1, Harunobu Kagawa2

  • 1Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single-cell Omics (LISCO), KU Leuven-University of Leuven, 3000 Leuven, Belgium.

Cell Stem Cell
|September 2, 2022
PubMed
Summary

Researchers developed a method to model human extraembryonic mesoderm cells (EXMCs) in vitro, offering new insights into early human embryogenesis and related developmental defects.

Keywords:
extraembryonic mesodermhuman blastoidshuman embryoshuman naive pluripotent stem cells

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Human Embryogenesis

Background:

  • Primate postimplantation embryogenesis involves extraembryonic mesoderm (EXM) specification before gastrulation, unlike rodents.
  • Human pluripotent stem cells (hPSCs) offer a model system for studying early developmental processes.

Purpose of the Study:

  • To investigate the potential of naive hPSCs to differentiate into EXM cells (EXMCs).
  • To characterize the signaling pathways involved in EXMC specification and maintenance.
  • To compare in vitro-derived EXMCs with those found in early human and primate embryos.

Main Methods:

  • Inhibition of Nodal signaling and GSK3B to induce EXMC differentiation from hPSCs.
  • Maintenance of EXMCs using mTOR and BMP4 signaling.
  • Transcriptome and epigenome profiling of differentiated EXMCs.
  • Analysis of cell populations within human blastoids.

Main Results:

  • Naive hPSCs can differentiate into EXMCs.
  • EXMC specification is regulated by Nodal, GSK3B, mTOR, and BMP4 signaling.
  • In vitro-derived EXMCs share molecular similarities with embryonic EXM.
  • EXMCs can arise from an epiblast intermediate and exhibit self-renewal.
  • EXMCs constitute a significant portion of off-target cells in human blastoids.

Conclusions:

  • A robust in vitro model for primate-specific EXMC specification has been established.
  • This model facilitates the study of early human embryogenesis and associated defects.
  • Understanding EXMC formation is crucial for interpreting blastoid development and potential off-target cell populations.