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Updated: Sep 25, 2025
12:12
In vivo Reprogramming of Adult Somatic Cells to Pluripotency by Overexpression of Yamanaka Factors
Published on: December 17, 2013
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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
Summary
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.
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.
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