Another role of sirtuin-1

Induced pluripotent stem cells need the SIRT1 protein

NanoNewsNet based on CNIO materials: A protein required for integrity of induced pluripotent stem cells

Reprogramming transforms specialized cells, such as neurons or fibroblasts, into cells that have the properties of embryonic stem cells. Reversing the evolutionary development of cells requires reversing the biology of their telomeres – structures that protect the ends of chromosomes. While under normal conditions, telomeres shorten over time, when reprogrammed, they follow the opposite strategy and lengthen.

A study published in the journal Stem Cell Reports (De Bonis et al., SIRT1 Is Necessary for Proficient Telomere Elongation and Genomic Stability of Induced Pluripotent Stem Cells) shows that during reprogramming, cells need the SIRT1 protein to lengthen and preserve telomeres. In addition, SIRT1 guarantees the integrity of the genome of stem cells obtained by reprogramming – the so-called induced pluripotent stem cells (iPSCs).

The study was conducted by a group of scientists studying telomeres and the enzyme telomerase at the Spanish National Cancer Research Center (Centro Nacional de Investigaciones Oncologicas, CNIO).

Since the Japanese scientist Shinya Yamanaka, now a Nobel laureate, first obtained iPS cells from specialized adult tissue in 2006, regenerative medicine has become one of the most interesting and rapidly developing areas of biomedicine. Given the ability to differentiate iPS cells into any type of cell, she sets herself an ambitious goal - to regenerate organs damaged by diseases such as Alzheimer's disease, diabetes or cardiovascular diseases.

However, there are ongoing disputes around the properties of induced pluripotent cells. Recent studies show that chromosomal aberrations and DNA damage can accumulate in these cells.
"The problem is that we don't know if these cells are really safe," explains postdoctoral researcher Maria Luigia De Bonis, the first author of the study.

In 2009, the same CNIO laboratory found that telomere length increases during reprogramming (Marion et al., Cell Stem Cell 2009), which is very important, since it allows stem cells to become immortal – to acquire one of their most significant properties.

A year later, it was shown that the levels of SIRT1, a protein belonging to the sirtuins family, involved in the preservation of telomeres, maintaining genome stability and responding to DNA damage, were increased in embryonic stem cells. Researchers from CNIO asked the question: does SIRT1 participate in cell reprogramming?

Using mouse models and cell cultures with SIRT1 removed as research tools, scientists have established that this protein is necessary for correct and safe reprogramming.

"We observed cell reprogramming in the absence of SIRT1, but over time, the resulting iPS cells lengthened their telomeres less efficiently and suffered from chromosomal aberrations and DNA damage," de Bonis comments. "SIRT1 helps iPS cells stay healthy."

Chromosomal abnormalities in reprogrammed cells with the SIRT1 protein removed (shown in red)
Photo: Centro Nacional de Investigaciones Oncologicas

The authors have deciphered the molecular mechanism of this protective effect for pluripotent stem cells, partially mediated by the regulatory protein SMUs. SIRT1 slows down the degradation of SMUs, which leads to an increase in the level of the enzyme in cells that increases the length of telomeres– telomerase.

A study by Spanish scientists sheds light on how reprogramming ensures the normal functioning of stem cells. This information will help to overcome the barriers that stand in the way of the use of induced pluripotent cells in regenerative medicine.

Portal "Eternal youth" http://vechnayamolodost.ru24.04.2014