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mTOR activity paces human blastocyst stage developmental progression.

Dhanur P Iyer1, Heidar Heidari Khoei2, Vera A van der Weijden3

  • 1Stem Cell Chromatin Group, Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.

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|September 27, 2024
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Summary
This summary is machine-generated.

Human cells can enter a dormant state, similar to other mammals, by regulating the mTOR pathway. This discovery in human pluripotent stem cells and blastoids has implications for reproductive therapies.

Keywords:
blastoiddevelopmentdiapausedormancyhumanmTORpluripotent stem cells

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Area of Science:

  • Reproductive biology
  • Developmental biology
  • Stem cell research

Background:

  • Mammalian embryos can pause development (embryonic diapause) to synchronize conception with optimal conditions for parturition.
  • In mice, embryonic diapause is regulated by the mTOR signaling pathway, but its conservation in humans is unknown.

Purpose of the Study:

  • To investigate if human pluripotent stem cells (hPSCs) and blastoids can enter a dormant state analogous to embryonic diapause.
  • To determine the role of the mTOR signaling pathway in regulating this dormant state in human cells.

Main Methods:

  • hPSCs and blastoids were treated to decrease mTOR signaling pathway activity.
  • Cellular proliferation, developmental progression, and attachment capacity to endometrial cells were assessed.
  • Reversibility of the dormant state was evaluated at functional and molecular levels.

Main Results:

  • Decreased mTOR signaling induced hPSCs and blastoids to enter a dormant state.
  • This dormancy was characterized by limited proliferation, developmental progression, and endometrial cell attachment.
  • The dormant state was found to be reversible at both functional and molecular levels.

Conclusions:

  • Human cells, like those of other mammals, possess the ability to enter a reversible dormant state around the blastocyst stage.
  • Regulation of the mTOR signaling pathway is key to inducing and potentially reversing this dormancy in human cells.
  • This finding has significant potential implications for advancing human reproductive therapies.