May 4, 2018

Researchers clarify the identity of adult brain stem cells

UCalgary study offers important insights into how neural stem cells are regulated

Author

Collene Ferguson, Faculty of Veterinary Medicine

Research by Jeff Biernaskie, University of Calgary Faculty of Veterinary Medicine, and postdoctoral fellow Jo Anne Stratton sheds important new light on the identity of the cells that exhibit neural stem cell function.  A paper on their work, with co-lead author Prajay Shah (not pictured), is published in the May 3 edition of Cell.

Jeff Biernaskie, Faculty of Veterinary Medicine, and postdoctoral fellow Jo Anne Stratton.

The human nervous system is a complex structure that sends electrical signals from the brain to the rest of the body, enabling us to move and think. Unfortunately, when brain cells are damaged by trauma or disease, they don’t automatically regenerate. This can lead to permanent disability.

However, within the brain, there are a small number of stem cells that persist into adulthood, offering a possible source of new cells to repair the damaged brain. Work by researchers at the University of Calgary Faculty of Veterinary Medicine sheds new light on the identity of the cells that exhibit neural (brain) stem cell function.

One type, astrocyte neural stem cells, can self-renew and generate new neurons, particularly following brain injury.

The other type — called ependymal cells — provide a supportive lining between the brain and the fluid that bathes the brain.

“Importantly, ependymal cells that line the caverns of the brain (called ventricles) also sit right next to neural stem cells, suggesting that they might be important regulators of neural stem cell function,” says senior author on the study Jeff Biernaskie, PhD, Calgary Firefighters Burn Treatment Society Chair in Skin Regeneration and Wound Healing, and associate professor of stem cell biology in the Faculty of Veterinary Medicine.

Study provides new insights into how brain cells work

“However, several high-profile studies have suggested that ependymal cells can actually become neural stem cells themselves, when activated by an injury to the brain. Our work provides evidence this is not the case and provides new insight into how they might contribute to brain function.”

In this study, the researchers developed a process allowing them to specifically label ependymal cells within the adult brain, while avoiding astrocyte stem cells. To their surprise, after tracking these cells over several months in either the normal or injured brain, they failed to find any instances of ependymal cell division or new neurons being generated from the ependymal cells (hallmark features of a neural stem cell).

By performing an extensive gene expression analysis of thousands of individual cells from the adult brain, they were able to directly compare ependymal cells to astrocyte neural stem cells.

“Interestingly, we discovered that although there are surprisingly many similarities between ependymal cells and resting neural stem cells, there are distinct differences in gene expression pattern that likely underlie ‘stemness’.”

Model could be an important tool towards better understanding brain cell dysfunction

Biernaskie says the research not only clarifies the identity of the adult neural stem cell, it also provides a new model to study the function of ependymal cells and their role in maintaining normal brain function.

“We hope the model we have developed will be an important tool toward understanding the impact of ependymal cell dysfunction during both brain development and in the onset of neurodegenerative diseases.”

The research paper is published in the May 3rd edition of the journal Cell. Co-lead authors on the study are Prajay Shah and Jo Anne Stratton. Also contributing to the paper were Morgan Stykel, Sepideh Abbasi, Sandeep Sharma, Kyle Mayr, Kathrin Koblinger and Patrick Whelan, researchers with the Hotchkiss Brain Institute’s Spinal Cord/Nerve Injury and Pain NeuroTeam.

The work was funded by Canadian Institutes of Health Research and the Calgary Firefighters Burn Treatment Society. Undergraduate studentships and a postdoctoral fellowship were provided by the Alberta Children’s Hospital Research Institute and Markin Undergraduate Research Program.

Jeff Biernaskie, PhD, is the Calgary Firefighters Burn Treatment Society Chair in Skin Regeneration and Wound Healing, and associate professor of stem cell biology at UCVM. He is also an associate professor in the Department of Surgery and a member of the Hotchkiss Brain Institute and the Alberta Children’s Hospital Research Institute at the Cumming School of Medicine.

Led by the Hotchkiss Brain Institute, Brain and Mental Health is one of six research strategies guiding the University of Calgary towards its Eyes High goals. The strategy provides a unifying direction for brain and mental health research at the university and positions researchers to unlock new discoveries and treatments for brain health in our community.