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Related Experiment Video

Updated: Nov 10, 2025

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
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An Esrrb and Nanog Cell Fate Regulatory Module Controlled by Feed Forward Loop Interactions.

Ana Sevilla1,2,3, Dimitri Papatsenko1,2, Amin R Mazloom4

  • 1Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Frontiers in Cell and Developmental Biology
|April 5, 2021
PubMed
Summary
This summary is machine-generated.

Estrogen related receptor beta (Esrrb) depletion in mouse embryonic stem cells reveals a regulatory network. This network, involving Nanog and Esrrb, controls the timing of cell fate decisions during development.

Keywords:
epigeneticsfeed forward regulatory loopsmulti-omics networkproteomicsstem cells

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Molecular Regulatory Mechanisms

Background:

  • Cell fate decisions are complex, involving multiple regulatory layers like chromatin remodeling, DNA methylation, and transcription factor binding.
  • The precise coordination of these regulatory dimensions in guiding developmental cell fate remains poorly understood.
  • Estrogen related receptor beta (Esrrb) is a known key regulator of pluripotency in mouse embryonic stem cells (mESCs).

Purpose of the Study:

  • To quantify multi-dimensional molecular changes in mESCs following the depletion of the pluripotency regulator Esrrb.
  • To elucidate the regulatory mechanisms coordinating cell fate decisions by comparing Esrrb and Nanog depletion effects.
  • To propose a hierarchical model for pluripotency maintenance and differentiation timing.

Main Methods:

  • Quantitative analysis of multi-dimensional molecular changes in mESCs.
  • Comparative gene expression analysis after depleting Esrrb and Nanog.
  • Meta-analyses of regulatory interactions.

Main Results:

  • Depletion of Esrrb in mESCs triggers significant multi-dimensional molecular alterations.
  • Comparative analysis revealed interlocked feed-forward loops between Nanog and Esrrb are crucial for regulating the timing of mESC fate decisions.
  • Oct4-Sox2 module maintains pluripotency, while the Nanog-Esrrb module governs differentiation timing.

Conclusions:

  • A hierarchical regulatory model explains pluripotency maintenance and differentiation timing in mESCs.
  • The Nanog-Esrrb module plays a critical role in timing developmental cell fate decisions.
  • Understanding these regulatory networks is key to deciphering developmental processes.