Zscan4 Expression Enhances Genome Stability and Telomere Length
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Solution Overview
Problem
The mechanism by which mouse embryonic stem (ES) cells maintain genomic stability is poorly understood, and existing methods for telomere elongation in ES and induced pluripotent stem (iPS) cells are not effective in promoting genome stability and telomere length.
Innovation Solution
Increasing the expression of Zscan4 in ES or iPS cells using an isolated nucleic acid molecule encoding Zscan4, which enhances genome stability and telomere length by promoting telomere recombination and reducing chromosome abnormalities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing methods for telomere elongation are used in ES and iPS cells, then telomere length may be maintained, but genome stability is not effectively promoted
Solution Approach 1:
The invention changes the biological parameter of Zscan4 expression level in ES and iPS cells. By introducing an isolated nucleic acid molecule encoding Zscan4, the expression of this gene is increased, which simultaneously promotes both telomere elongation and genome stability, resolving the contradiction between maintaining telomere length and promoting genome stability
Solution Approach 2:
Zscan4 acts as an intermediary molecule that mediates between telomere maintenance and genome stability. The isolated nucleic acid molecule encoding Zscan4 serves as a mediator that introduces this protective function into ES and iPS cells, enabling both telomere elongation and enhanced genome stability through a single molecular intervention
2Duration of action of moving object
If mouse ES cells are cultured for long-term proliferation, then self-renewal capacity is maintained, but chromosomal abnormalities increase
Solution Approach 1:
The invention applies preliminary action by introducing the isolated nucleic acid molecule encoding Zscan4 into ES and iPS cells before chromosomal abnormalities can accumulate during long-term culture. This preventive measure establishes enhanced telomere maintenance and genome stability mechanisms in advance, allowing cells to proliferate for extended periods without acquiring chromosomal abnormalities
Solution Approach 2:
By introducing Zscan4 expression, the cells gain self-service capability for maintaining their own genomic integrity during long-term proliferation. The Zscan4 protein enables the cells to autonomously protect their chromosomes and maintain telomere length, allowing sustained self-renewal without external intervention or accumulation of chromosomal abnormalities
Data Source
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AI summary
The disclosure provides methods for increasing genome stability of an embryonic stem (ES) cell or induced pluripotent stem (iPS) cell, increasing telomere length in an ES or iPS cell, or both, for example by contacting an ES or iPS cell with an agent that increases expression of Zscan4 in the cell. Methods for increasing the genome stability in a population of ES or iPS cells, increasing telomere length in a population of ES or iPS cells, or both, are provided, for example by selecting Zscan4+ ES or iPS cells from the population of ES or iPS cells (which can include both Zscan4+ and Zscan4- ES or iPS cells). Therapeutic methods of using ES or iPS cells expressing Zscan4 are also provided. Further provided are methods of treating cancer by administering a Zscan4 polynucleotide or Zscan4 polypeptide. Also provided are methods of inducing differentiation of isolated ES or iPS cells into germ cells.