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Updated: Jun 13, 2026

Differentiation of Newborn Mouse Skin Derived Stem Cells into Germ-like Cells In vitro
Published on: July 16, 2013
Oocyte-type linker histone B4 is required for transdifferentiation of somatic cells in vivo
Nobuyasu Maki1, Rinako Suetsugu-Maki, Shozo Sano
1Department of Biology, University of Dayton, Dayton, OH 45469-2320, USA. makinobu@notes.udayton.edu
Abstract:
The ability to reprogram in vivo a somatic cell after differentiation is quite limited. One of the most impressive examples of such a process is transdifferentiation of pigmented epithelial cells (PECs) to lens cells during lens regeneration in newts. However, very little is known of the molecular events that allow newt cells to transdifferentiate. Histone B4 is an oocyte-type linker histone that replaces the somatic-type linker histone H1 during reprogramming mediated by somatic cell nuclear transfer (SCNT). We found that B4 is expressed and required during transdifferentiation of PECs. Knocking down of B4 decreased proliferation and increased apoptosis, which resulted in considerable smaller lens. Furthermore, B4 knockdown altered gene expression of key genes of lens differentiation and nearly abolished expression of gamma-crystallin. These data are the first to show expression of oocyte-type linker histone in somatic cells and its requirement in newt lens transdifferentiation and suggest that transdifferentiation in newts might share common strategies with reprogramming after SCNT.
Insights
Histone B4, an oocyte-type linker histone, is crucial for newt lens regeneration. Its expression in somatic cells is required for pigmented epithelial cell transdifferentiation, impacting cell proliferation and lens development.
Area of Science:
- Developmental Biology
- Cellular Reprogramming
- Molecular Biology
Background:
- In vivo somatic cell reprogramming after differentiation is challenging.
- Newt lens regeneration involves transdifferentiation of pigmented epithelial cells (PECs) to lens cells.
- Molecular mechanisms underlying newt transdifferentiation remain largely unknown.
Purpose of the Study:
- To investigate the molecular events involved in newt lens transdifferentiation.
- To determine the role of oocyte-type linker histone B4 in this process.
Main Methods:
- Studied the expression of Histone B4 during newt lens regeneration.
- Utilized knockdown techniques to assess the requirement of B4 in transdifferentiation.
- Analyzed cell proliferation, apoptosis, and gene expression changes post-B4 knockdown.
Main Results:
- Histone B4 is expressed and required for newt PEC transdifferentiation.
- B4 knockdown reduced cell proliferation, increased apoptosis, and resulted in smaller lenses.
- B4 knockdown altered key lens differentiation gene expression, including gamma-crystallin.
Conclusions:
- This study demonstrates the expression and requirement of an oocyte-type linker histone (B4) in somatic cells during newt lens transdifferentiation.
- Findings suggest that newt transdifferentiation shares molecular strategies with somatic cell nuclear transfer (SCNT) reprogramming.
- Histone B4 plays a critical role in regulating cell fate and development during regeneration.
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