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Microscopic Chromosomal Structural and Dynamical Origin of Cell Differentiation and Reprogramming.

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Summary

Cell differentiation and reprogramming involve significant changes in 3D genome architecture. A new model reveals distinct chromosomal structural pathways for embryonic stem cell (ESC) differentiation and somatic cell reprogramming.

Keywords:
cell developmentchromosome dynamicsenergy landscapenon‐equilibrium cell dynamics

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Area of Science:

  • Genomics
  • Cell Biology
  • Biophysics

Background:

  • Cell development relies on 3D genome architecture reorganization for gene regulation.
  • Understanding the physical basis of cell differentiation and reprogramming is crucial.

Purpose of the Study:

  • To develop a landscape-switching model for exploring chromosomal structural origins of cell differentiation and reprogramming.
  • To investigate the microscopic structural changes during embryonic stem cell (ESC) differentiation and somatic cell reprogramming.

Main Methods:

  • Development of a theoretical landscape-switching model.
  • Analysis of chromosomal structural changes, including compartment-switching and locus repositioning.
  • Inclusion of non-equilibrium effects in the theoretical model.

Main Results:

  • Chromosome structure exhibits compartment-switching within topologically associating domains.
  • ESC differentiation involves monotonic chromosome compaction, with active loci moving to the surface and inactive loci to the interior.
  • Somatic cell reprogramming shows an overexpanded chromosome with universal surface localization of loci, erasing somatic cell characteristics.
  • An early distinct differentiation pathway for ESCs is suggested, leading to bifurcation on the Waddington landscape.

Conclusions:

  • The model provides a physical understanding of cell differentiation and reprogramming from a chromosomal structural and dynamical perspective.
  • Cell differentiation and reprogramming processes are highly irreversible, consistent with experimental observations.
  • The findings offer testable predictions for future experimental validation.