German scientists have found that Akna protein regulates the regeneration of organs by stem cells. In addition, it controls the behavior of neural stem cells through a mechanism that can also be involved in the formation of metastases.
The research team headed by Prof. Dr. Magdalena Götz, director of the Institute for Stem Cell Research (ISF) at Helmholtz Zentrum München and Chair of Physiological Genomics of the Ludwig Maximilian University of Munich (LMU) Biomedical Center, wanted to identify factors that support functionality and regulate the differentiation of neural stem cells.
To do this, scientists have identified neural stem cells that either renew themselves and create additional stem cells or differentiate.
“We found that the Akna protein is present in higher concentrations in stem cells that generate neurons”, – explains ISF researcher German Camargo Ortega, first author of the study, which was published in the journal Nature. “Our experiments showed that low levels of the Akna protein cause stem cells to remain in the stem cell niche, whereas higher levels stimulate them to detach from the niche, thus promoting differentiation,”
Akna protein is known to be a transcription factor that binds to AT-rich regions of DNA (AT-hook), which regulates the transcription of one or more genes.
Scientists were surprised by the location of this protein in the centrosome – the organelle inside the cell, which serves as the chief architect in the organization of the cytoskeleton and regulates cell division.
“We discovered that an incorrect sequence was originally published for this protein”, – reports Sven Falk, first co-author of the study. “However, our work clearly showed that Akna is located directly at the centrosome.”
Scientists have shown that Akna regulates the organization of microtubules and their attachment to the centrosome, which leads to a weakening of the bonds of neighboring cells in the niche of stem cells and promotes their migration.
“Our experiments show that this function also plays an important role in a process known as epithelial-to-mesenchymal transition, or EMT for short”, – explains the study leader Magdalena Götz. “In this process, cells detach from a cluster, proliferate and begin to migrate. This occurs, for example when stem cells migrate to form new neurons, but it can also be harmful in disease, for example when cancer cells leave a tumor to form metastases elsewhere in the body. The novel mechanism that we identified by studying the function of Akna therefore appears to play a key role in a broad range of medically relevant processes.”
The next stage of research, scientists plan to devote to the study of the role of Akna in the functioning of other types of stem cells and the immune system.