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Cell-cell Fusion of Genome Edited Cell Lines for Perturbation of Cellular Structure and Function
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Adding a dimension to cell fate.

Tiziana A L Brevini1, Elena F M Manzoni1, Sharon Arcuri1

  • 1Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, Milano 20122, Italy.

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|December 10, 2020
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Summary

Small molecules and tissue-like substrates can reprogram adult fibroblasts into insulin-producing cells (EpiCC). Mechanical forces and Hippo signaling are key to this epigenetic reprogramming for regenerative medicine.

Keywords:
3D cultureepigenetic conversionmechano-sensing

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Area of Science:

  • Epigenetics and Mechanobiology
  • Cellular reprogramming and regenerative medicine

Background:

  • Epigenetic mechanisms and mechanical forces regulate cell fate, plasticity, and differentiation.
  • Microenvironment stiffness and 3D rearrangements influence cell potency and differentiation via mechanosensing pathways.

Purpose of the Study:

  • To present an overview of small molecules' role in modulating cell plasticity and fate.
  • To describe the conversion of adult dermal fibroblasts into insulin-producing cells (EpiCC) and examine the influence of substrate stiffness and the Hippo pathway.

Main Methods:

  • Utilized small molecules to erase epigenetic signatures of fibroblasts.
  • Cultured cells on substrates mimicking in vivo tissue stiffness.
  • Employed a transgenic fibroblast cell line (INS-eGFP) for real-time monitoring of cell conversion.

Main Results:

  • Successfully converted adult dermal fibroblasts into insulin-producing cells (EpiCC).
  • Demonstrated that tissue-like substrate stiffness enhances reprogramming efficiency.
  • Identified the Hippo signaling pathway as a key mediator in this mechanotransduction process.

Conclusions:

  • Small molecules and appropriate mechanical cues can reprogram cell fate, offering potential for regenerative medicine.
  • The INS-eGFP transgenic model facilitates real-time monitoring for scalable cell therapy development.
  • Reliable in vitro models are crucial for advancing regenerative medicine, reducing animal testing, and improving animal welfare.