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Related Concept Videos

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Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
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Related Experiment Video

Updated: Aug 19, 2025

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
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Synergistic activation of RARβ and RARγ nuclear receptors restores cell specialization during stem cell

Aysis Koshy1, Elodie Mathieux1, François Stüder1

  • 1UMR 8030 Génomique Métabolique, Genoscope, Institut François Jacob, CEA, CNRS, University of Evry-val-d'Essonne, University Paris-Saclay, Évry, France.

Life Science Alliance
|November 29, 2022
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Summary
This summary is machine-generated.

Synthetic agonists for retinoic acid receptors (RARs) promote nervous system cell specialization. RARβ and RARγ activation induces neuronal and glial subtypes, revealing RARα

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Area of Science:

  • Stem cell biology
  • Systems biology
  • Neuroscience

Background:

  • Understanding how external cues guide cell specialization into complex tissues is crucial.
  • Retinoic acid receptors (RARs) play a role in cell development and differentiation.
  • Embryonic carcinoma (P19) and mouse embryonic (E14) stem cells offer models for studying neural development.

Purpose of the Study:

  • To investigate the use of RAR-selective synthetic agonists for directing cell specialization in nervous tissue formation.
  • To elucidate the gene regulatory programs activated by these agonists.
  • To understand the interplay between different RAR isotypes in cell fate determination.

Main Methods:

  • Utilizing P19 and E14 stem cells treated with RAR-selective agonists (BMS641, BMS961).
  • Employing RAR isotype knockout lines to dissect the roles of individual RARs.
  • Performing global transcriptome analysis (RNA sequencing) and in silico modeling of gene regulatory networks.

Main Results:

  • Synergistic activation of RARβ and RARγ induces maturation into neuronal subtypes, astrocytes, and oligodendrocyte precursors.
  • RARα-driven gene programs are essential for neuronal specialization and are influenced by RARβ/RARγ activation.
  • Transcriptome landscaping and computational modeling revealed complex gene regulatory interactions.

Conclusions:

  • This study provides a systems biology perspective on RAR-mediated gene programs during neural development.
  • The findings explain previously observed functional redundancy among RAR isotypes.
  • The results suggest potential therapeutic strategies for directing cell specialization in nervous tissue formation.