Within the last decade, researchers have found that the adult brain can continue to generate neurons throughout life because of the presence of neural stem cells. However, this continued generation of neurons in the adult brain requires a sustained population of stem cells, which relies on a regulated balance of cell fate decisions. Thus understanding the regulation of stem cell maintenance is key to preventing stem cell depletion and aging.
Recently, Professor Dr. Ruth Slack and Postdoctoral Fellow Dr. Mireille Khacho from the University of Ottawa Faculty of Medicine’s Department of Cellular and Molecular Medicine and University of Ottawa’s Brain and Mind Research Institute (uOBMRI), have made an important discovery that uncovers a major role for mitochondria in stem cell fate decisions, which has been recently published in a paper in Cell Stem Cell.
The members of Dr. Slack’s lab, along with researchers from Johns Hopkins University and l’Université du Québec à Trois-Rivières, studied mitochondria and stem cells to understand exactly how to maintain and regenerate the pool of stem cells in the adult brain, as well as the mechanism behind stem cell maintenance. In particular, what determines a stem cell’s decision to become a neuron or remain a stem cell? They found their answer in mitochondria.
Mitochondria are the energy factories of a cell. However, it was previously thought that mitochondria do not function in stem cells. Dr. Mireille Khacho, the first author of the study, found that within the stem cell population, mitochondria are actually able to dictate stem cell fate, a function never before ascribed to these organelles. It was discovered that mitochondria in stem cells have a certain shape that regulates their identity, and when the shape of mitochondria changes this relays a message within stem cells that will activate the formation of neurons. That these energy factories can modify stem cell fate is quite a surprise.
The preservation of stem cells relies on the regulation of cell fate decisions, an imbalance of which can have detrimental effects. “As stem cells are extremely sensitive to these changes,” Dr. Slack explains, “disruptions or imbalances may cause depletion of the stem cell pool in the adult brain.” This change is implicated in aging and a number of diseases, including neurodegenerative diseases such as Parkinson's, stroke and Alzheimer's as well as a host of metabolic disorders.
Dr. Slack’s study is the first to examine mitochondrial influence on the maintenance and regeneration of the stem cell pool in the brain.
“To date,” says Dr. Mireille Khacho, “in instances of neurodegenerative disease, everyone has believed that the defect is solely located within in the neurons. However, we have shown that there can also be a defect in the stem cells, and that the stem cell could in fact be the origin of many of these neurodegenerative diseases.”
The team conducted tests on a number of models, disrupting the mitochondria within the stem cell. What they found opened a completely new area of study, as the disruption led to cognitive decline in memory and learning tests.
The implications of this finding are far-reaching as the maintenance of the stem cell pool is essential throughout life. Researchers can now understand some of the reasons why stem cells don’t always replenish in the adult brain.
“Our findings have opened up a legion of new and exciting questions,” said Dr. Slack.
Dr. Slack’s laboratory focuses on the field of neural regeneration, investigating developmental pathways and exploring the potential for future therapeutic targets. For more information about Dr. Slack’s lab, please visit her page on the Faculty’s website.
To read the full paper, please visit the Cell Stem Cell Website