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Updated: Jul 7, 2026
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Cell-cell Fusion of Genome Edited Cell Lines for Perturbation of Cellular Structure and Function
Published on: December 7, 2019
Cell fusion-mediated nuclear reprogramming of somatic cells
Hiroyuki Matsumura1, Takashi Tada
1Laboratory of Stem Cell Engineering, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. ttada@frontier.kyoto-u.ac.jp
Reproductive Biomedicine Online
|February 7, 2008
Summary
Embryonic stem cells (ESCs) can reprogram somatic cell nuclei. A new method uses chromosome elimination to create personalized stem cells, demonstrating that reprogrammed somatic factors maintain pluripotency for therapeutic applications.
Area of Science:
- Stem cell biology
- Reproductive medicine
- Genetics
Background:
- Embryonic stem cells (ESCs) exhibit nuclear reprogramming capabilities via cell fusion.
- Personalized stem cell generation is advanced by technologies like cytoplasmic cell fusion and ES cell factor introduction.
- Targeted chromosome elimination from ESCs is a novel approach for creating personalized stem cells.
Purpose of the Study:
- To develop and validate a targeted chromosome elimination technology for producing personalized stem cells.
- To assess the role of ESC-derived chromosomes in maintaining pluripotency after somatic cell reprogramming.
- To explore the therapeutic potential of personalized stem cell populations.
Main Methods:
- Development of a universal chromosome elimination cassette (CEC) conferring drug resistance and GFP fluorescence, flanked by loxP sites.
- Hybridization of GFP-positive ESCs (with CEC-integrated chromosome) with adult thymocytes.
- Induction of sister chromatid recombination and targeted chromosome loss using Cre recombinase, leading to GFP-negative cells.
Main Results:
- Successful elimination of the CEC-tagged chromosome from hybrid cells upon Cre recombinase exposure.
- Demonstration that targeted elimination of ESC-derived chromosome 6s does not impair pluripotency.
- Confirmation that reprogrammed somatic factors are sufficient for maintaining pluripotentiality in hybrid cells.
Conclusions:
- Targeted chromosome elimination technology is effective for generating personalized stem cells.
- This method facilitates the development of major histocompatibility complex-personalized or fully personalized stem cell populations.
- The technology holds promise for diverse therapeutic applications requiring tailored stem cells.
Related Concept Videos
01:24Methods of Nuclear Reprogramming
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for injury repair.
01:14Introduction to Nuclear Reprogramming
Nuclear reprogramming is the process of switching gene expression of one cell type to that of another cell type, usually from a differentiated cell state to an undifferentiated cell state. Differentiation occurs during processes such as development and morphogenesis, tissue regeneration, and malignancy. Cells can also be artificially induced to reprogram their gene expression by techniques such as nuclear transfer, induced pluripotency, and cell fusion. Such techniques have many applications in...
01:29Somatic to iPS Cell Reprogramming
Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012 for this...
01:32Chromatin Modification in iPS Cells
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
02:53Conservative Site-specific Recombination and Phase Variation
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
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01:30Crossing Over
Crossing over is the exchange of genetic information between homologous chromosomes during prophase I of meiosis I. Genetic recombination gives rise to allelic diversity in the newly formed daughter cells. In humans, crossing over produces genetically distinct haploid egg and sperm cells that undergo fertilization to produce unique offspring. Before cell division starts, the germ cell’s chromosome(s) undergo duplication in the S phase of the cell cycle. As the cells enter prophase I, duplicated...