Stem Cell Research in Mice Suggests Ways to Solve Biomarker Problems in Blood
NEW YORK-Researchers have discovered how to coax stem cells to differentiate into less specialized cells that could better serve as the basis for anti-ageing tissues (hematopoietic). The discovery could guide the quest to find a replacement for senescent cells long thought to be the source of age-related disease which now affects more than 8 out of 10 American adults and is associated with a higher risk for cardiovascular disease and heart disease. The study was conducted by investigators at The Rockefeller University and published in Genes Development on April 8 2020.
Stem cells are in high demand given their ability to donate their precursors-endothelial cells-for regenerative therapeutics laboratory applications and muscle transplantation. While stem cells harboring specific gene profiles have been shown to be sufficient for healthy adult development in disease progression they can transform into cells with abnormal altered or defective genes. In normal a fetal stem cell can divide for up to 24 months. Prior clinical studies have demonstrated that adult stem cells display a greater capacity to differentiate into blood-forming cells (BBCs). Previously however it has been suggested that variations in genetic oncogenesis may be a sign of telomere-related neurodegeneration a disease in which cells lose the ability to divide and remain in differentiated amorphous states.
It is known that telomere factors reside on the ends of chromosomes in the nucleus of most mature cells and that these telomeres shorten in length with each cell cycle (called telomeosis). In spite of a long stretch of research it has been assumed that telomere factor effects and telomeres are strictly controlled by the evolutionary pressures of the cell. That is as DNA repair mechanisms are activated telomeres shorten.
Recipes for telomere maintenance.
To address this question the team led by Domene Gran Barrera-Huetos PhD sought to explore the mechanisms of telomere maintenance in an adult cell using the mouse as a model to investigate telomeres at both the triple-negative (matrix) as well as the mesenchymal stem cell (MSC).
To this end an established method of mouse retinylated foxhope reporter (RPR) assays were used. Adenosine-3-phosphate receptors (ATRs) are well established protection molecules that bind to the extracellular matrix of endothelial cells. To test whether there was an effect of RPRs on telomere length cells were treated with various concentrations of RPRs. Surprisingly RPRs (9-15 gml) were not reduced in length in all the cells analyzed. Furthermore RPR stimulation at levels found in the decided tissue delayed telomere length by 20-30 m (s). The lengthened telomere also proved to be associated with an altered histone transcription factor VEGF-3 expressed in pericytes and mitochondria of the BM including in the endothelial cells.
Gran Barrera-Huetos noted that previous studies have shown that telomere long-term effects appear to be driven by epigenetic factors. DNA repair pathways are activated by epigenetic factors released by activated satellite DNA chromosomes from their native locations in chromosomes she said. These factors which permit telomere elongation impair the telomere maintenance processes. Our study reveals that DNA reactivation in prefenced WT3 TTR- promoter regions ensures telomere elongation and proper cell differentiation.