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The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
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The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
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Updated: Sep 25, 2025

In vivo Reprogramming of Adult Somatic Cells to Pluripotency by Overexpression of Yamanaka Factors
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In vivo partial cellular reprogramming enhances liver plasticity and regeneration.

Tomoaki Hishida1, Mako Yamamoto2, Yuriko Hishida-Nozaki2

  • 1Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Laboratory of Biological Chemistry, School of Pharmaceutical Sciences, Wakayama Medical University, 25-1 Shitibancho, Wakayama, Wakayama 640-8156, Japan.

Cell Reports
|April 27, 2022
PubMed
Summary
This summary is machine-generated.

Mammals can enhance liver regeneration by partially reprogramming adult liver cells (hepatocytes) using the four Yamanaka factors (4F). This cellular plasticity approach shows promise for counteracting liver failure.

Keywords:
CP: Stem cell researchdedifferentiationliverregenerationreprogramming

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Area of Science:

  • Regenerative Medicine
  • Cellular Reprogramming
  • Hepatology

Background:

  • Mammalian regenerative capacity is limited compared to vertebrates like fish and salamanders.
  • Efficient regeneration in some species relies on cell dedifferentiation and proliferation.

Purpose of the Study:

  • To investigate if inducible expression of Yamanaka factors (4F) in mouse hepatocytes can enhance liver regeneration.
  • To explore the mechanisms of partial reprogramming in vivo.

Main Methods:

  • Generation of a mouse model for inducible expression of Oct-3/4, Sox2, Klf4, and c-Myc (4F) in hepatocytes.
  • Analysis of differentiated hepatic markers, proliferation markers, chromatin modifiers, and DNA accessibility.
  • Assessment of liver stem and progenitor cell markers post-4F expression.

Main Results:

  • Transient in vivo 4F expression induced partial reprogramming of hepatocytes to a progenitor state.
  • Observed increased cell proliferation, reduced differentiated markers, and altered DNA accessibility.
  • Demonstrated enhanced liver regenerative capacity via topoisomerase2-mediated reprogramming.

Conclusions:

  • Liver-specific 4F expression induces cellular plasticity and improves regeneration in mice.
  • Partial reprogramming offers a potential strategy for counteracting liver failure and enhancing tissue repair.