Common Telomere changes during In Vivo Reprogramming, and early stages of tumorigenesis
Recent studies have shown that mice can be reprogrammed to produce induced pluripotent cells. Telomeres determine the organism’s life span and are crucial for chromosomal stabilization. We investigate whether the changes in telomeres that occur during tissue dedifferentiation caused by in vivo reprograming are also reflected on the tissue. Telomerase-dependent telomere lengthening is observed in the reprogrammed regions. In the reprogrammed regions, the TRF1 protein was highly expressed, and this expression was independent of telomere size. TRF1 inhibitors reduced the in vivo efficiency of reprogramming. We extend our finding of TRF1 activation to tissue dedifferentiation in neoplasias. This is particularly true during pancreatic metaplasia (acinar to ductal metaplasia), a process which involves the transdifferentiation from adult acinar to ductal cells due to KRAS oncogene. Telomeres are important in cell plasticity during in vivo reprogramming as well as in pathological conditions that increase plasticity such as cancer.
Keywords: in vivo reprogramming, telomeres, stem cells, TRF1, tumorigenesis, cellular plasticity, cancer, transdifferentiation, ADM, regeneration.
In vivo, reprogramming to full pluripotency was achieved using mouse tissues (Abad and colleagues, 2013). Induction of reprogramming factor in transgenic mice, (so called reprogrammable mouse) leads to reprogramming marked by expression of NANOG, the pluripotency gene, in multiple organs and tissue dedifferentiation. Teratomas are also formed. These mice may be used to better understand the molecular mechanisms governing tissue dedifferentiation. It is interesting to note that mammalian cells can reprogramme themselves spontaneously after an injury or damage (Yanger and colleagues, 2013). In vivo, differentiated cells can be transformed into another cell type as well as functional multipotent stem cells (Tata and colleagues, 2013). This ability of somatic stem cells to dedifferentiate in vivo into multipotent stem-like cell types may play a crucial role in tissue regeneration and tumorigenesis.
Source:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312258/
