Cellular reprogramming can counteract aging that leads to a decrease in the activities and functions of the mesenchymal stem / stromal cells (MSc). This is something that scientists have known for a while. But what they did not discover is that nuclear mechanisms are responsible for this change. In a study published today Stem cell This mystery seems to have been solved. It not only enhances the knowledge of MSc aging and associated diseases, but also gives insight into developing pharmacological strategies to reduce or reverse the aging process.
The research team, made up of scientists from the University of Wisconsin-Madison, relied on cellular reprogramming – cellular reprogramming to establish a genetically identical young and old cell model for this study – a commonly used approach. “Agreeing with previous findings of MSc rejuvenation through cellular reprogramming, our study proceeds to provide an understanding of how molecules are regulated to satisfy cellular hallmarks of aging,” said Yi-Ju Li, Ph.D. Explains. Faculty member in the Department of Orthopedics and Rehabilitation and the Department of Biomedical Engineering.
When the age of the mesenchymal stem / stromal cells (MSc), the transcription factor GATA is used to induce the aging response. Through transcription factor-based cellular reprogramming, the aged MSc is rejuvenated with a reduction in GATA 6 effect on cellular aging. Credit: Alphamed Press
Researchers Began extracting from human synovial fluid (SF-MSC) – i.e., fluid found in the knee, elbow and other joints – and reprogramming it into induced pluripotent stem cells (IPSC). Then they did this IPSC. M.Sc. Turned into, with effect M.Sc. “When we compared the reprogrammed MSc with the non-functional parental MSc, we found that aging-related activities were much less in the reprogrammed MSc than in their parental line. This cell signals a reversal of aging, ”said Li. Lee said.
The team then analyzed the cells to determine if there was a change in global gene expression as a result of re-programming. They found that the expression of GAT6, a protein that plays an important role in the development of the intestines, lungs, and heart, was more stressful in regenerative program cells than in control cells. This suppression led to an increase in the activity of proteins needed for fetal development called sonic hedgehog (SHH) as well as expression levels of other proteins, Foxp1, needed for proper development of the brain, heart and lungs. “Thus, we identified the GAT6 / SHH / FoxP1 route as the main mechanism by which MSc controls aging and rejuvenation.”
“The identification of the GATA6 / SHH / FOXP1 route is a very important achievement in controlling the aging of MSc.” Dr. Jain Nolta, Editor-in-Chief Stem cell. “Premature aging can impair the ability of these promising cells to expand while retaining function for clinical use, and extensive knowledge of the ways in which they differentiate and control sensation is invaluable.”
To determine which Yamanaka transcription factors (the four reprogramming genes used to obtain IPSC) were involved in suppressing GATA6 in IPSC, the team analyzed the GATA6 expression in response to the knockdown of each factor. It was reported that only OCT4 and KLF4 are able to control GAT6 activity, which is consistent with some previous studies.
“Overall, we were able to demonstrate that cellular reprogramming results in significant changes in SF-MSC properties and functions. IPSC-M.Sc. This change in indicates the aggregation of cell aging. Most notably, we were able to identify the GATA 6 / SHH / FoxP1 signaling pathway as an underlying mechanism controlling cell aging-related activities, ”said Dr. Lee.
“We believe our findings will help us understand the importance of MSc in aging and regenerative medicine.”
Reference: Hongli Jiao, Brian E. Walkzak, Ming – Song Lee, Madeleine E. “GATA 6 regulates the aging of human mesenchymal stem / stromal cells” by Lamiax and Van-Ju Lee, 30 November 2020. Stem cell.
DOI: 10.1002 / stem.3297
