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Published on: December 7, 2019
Chromosomal and telomeric reprogramming following ES-somatic cell fusion
Huseyin Sumer1, Craig Nicholls, Alexander R Pinto
1Monash Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton, Victoria, 3168, Australia. huseyin.sumer@med.monash.edu.au
Chromosoma
|November 12, 2009
Summary
Cell fusion between embryonic stem cells and fibroblasts reprograms cells, increasing telomere length and activity without altering key telomerase gene expression. This finding offers a new model for telomere maintenance research.
Area of Science:
- Cell Biology
- Genetics
- Molecular Biology
Background:
- Embryonic stem (ES) cells possess pluripotency and high telomerase activity.
- Somatic cells, like mouse embryonic fibroblasts, have limited proliferative potential and shorter telomeres.
- Cell fusion is a method to investigate cellular reprogramming and genetic interactions.
Purpose of the Study:
- To investigate chromosomal and telomeric reprogramming following the fusion of ES cells and mouse embryonic fibroblasts.
- To assess the pluripotency and telomere maintenance mechanisms in the resulting hybrid cells.
- To identify potential regulators of telomere lengthening in hybrid cell models.
Main Methods:
- Fusion of mouse embryonic stem cells with mouse embryonic fibroblasts.
- Ploidy analysis using DNA profiling.
- Microsatellite polymerase chain reaction for chromosomal integrity assessment.
- Gene expression analysis for telomerase subunits (TERT, TERC, dyskerin).
- Antibody staining for pluripotency markers (Oct4, SSEA-1).
- Teratoma formation assay to evaluate pluripotency.
Main Results:
- Hybrid clones exhibited tetraploid or near-tetraploid DNA profiles.
- No significant random loss of somatic chromosomes was observed.
- ES-somatic hybrids retained pluripotency, forming teratomas with derivatives of all three germ layers.
- High telomerase activity and increased telomere lengths were detected in ES-somatic hybrids.
- No significant increase in the expression of TERT, TERC, or dyskerin was found, despite increased telomerase activity.
Conclusions:
- Cell fusion can induce significant telomeric reprogramming, leading to telomere lengthening.
- Telomere maintenance activation in these hybrids is not dependent on increased expression of critical telomerase subunits.
- The findings suggest that reprogramming involves the elimination of negative regulation of telomerase activity.
- This study presents the first evidence of telomere lengthening via cell fusion, establishing a novel model for telomere biology research.
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