Posted on Mar 27, 2018, 12 a.m.
Resting neural stem cells store clumps of proteins in specialized compartments called lysosomes, researchers from Stanford University School Of Medicine have found that clearing the clumps boosts their activity, as published in Science.
With aging cells become less proficient at disposing of protein aggregates, and ability to respond to make new neurons signal declines. Restoring lysosomes ability to function normally was shown to rejuvenate cell ability to active.. Discovery of aggregates in young stem cells was surprising as similar aggregates are associated with development of neurodegenerative diseases, it also shows how important it is to maintain control over protein production and disposal process throughout life and neural stem cell activation status.
Researchers investigated the differences between gene expression profiles of stem cells activated in response to signal to launch process to make new neurons and resting neural stem cells; and compared how the cells change with age.
Several populations of cells were isolated for study from brains of old and young mice which included resting neural stem cells and neural cell progenitors which arise from activated stem cells. It was found that lysosome associated genes were expressed by resting stem cells, and proteasome genes associated with protein complex involved in protein destruction were expressed by activated stem cells. Strict control of disposal and production allows cells to maintain inventory to carry out cellular functions.
Staining neural stem cells with a dye that binds to protein aggregate surprisingly showed that resting stem cells stained the brightest despite the fact they have lower rate of protein production. Accumulation of these protein aggregates in their lysosomes were observed to be slower in young resting neural stem cells as comparison to activated counterparts. Older resting stem cells expressed fewer lysosome associated genes and accumulate higher levels of aggregates. It was found that clearing the older cell artificially by either activating lysosomes or subjecting them to starvation conditions to limit protein production restored ability of older resting stem cells to activate.
Researchers plan to continue their investigations to learn what type of proteins contribute to aggregates to gain better understanding of why activated neural stem cells appear to favour proteasomes over lysosomes; and to determine how regulation of protein aggregation disrupts during aging.
Materials provided by Stanford Medicine.
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Dena S. Leeman, Katja Hebestreit, Tyson Ruetz, Ashley E. Webb, Andrew Mckay, Elizabeth A. Pollina, Ben W. Dulken, Xiaoai Zhao, Robin W. Yeo, Theodore T. Ho, Salah Mahmoudi, Keerthana Devarajan, Emmanuelle Passegué, Thomas A. Rando, Judith Frydman, Anne Brunet. Lysosome activation clears aggregates and enhances quiescent neural stem cell activation during aging. Science, 2018 DOI: 10.1126/science.aag3048