Summary: Researchers report ependymal cells may play an important role in the regulation of neural stem cell function.
Source: University of Calgary.
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.
Funding: 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.
Source: Collene Ferguson – University of Calgary
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Single-Cell Transcriptomics and Fate Mapping of Ependymal Cells Reveals an Absence of Neural Stem Cell Function” by Prajay T. Shah, Jo A. Stratton, Morgan Gail Stykel, Sepideh Abbasi, Sandeep Sharma, Kyle A. Mayr, Kathrin Koblinger, Patrick J. Whelan, and Jeff Biernaskie in Cell. Published May 3 2018.
Single-Cell Transcriptomics and Fate Mapping of Ependymal Cells Reveals an Absence of Neural Stem Cell Function
•High-fidelity genetic labeling and analysis of ependymal cells in the adult V-SVZ
•Ependymal cells are transcriptionally distinct from neural stem cells
•Ependymal cells express cilia genes (e.g., FoxJ1), not angiogenic genes (e.g., Flt1)
•Ependymal cells don’t behave as neural stem cells or progenitors in vitro or in vivo
Ependymal cells are multi-ciliated cells that form the brain’s ventricular epithelium and a niche for neural stem cells (NSCs) in the ventricular-subventricular zone (V-SVZ). In addition, ependymal cells are suggested to be latent NSCs with a capacity to acquire neurogenic function. This remains highly controversial due to a lack of prospective in vivo labeling techniques that can effectively distinguish ependymal cells from neighboring V-SVZ NSCs. We describe a transgenic system that allows for targeted labeling of ependymal cells within the V-SVZ. Single-cell RNA-seq revealed that ependymal cells are enriched for cilia-related genes and share several stem-cell-associated genes with neural stem or progenitors. Under in vivo and in vitro neural-stem- or progenitor-stimulating environments, ependymal cells failed to demonstrate any suggestion of latent neural-stem-cell function. These findings suggest remarkable stability of ependymal cell function and provide fundamental insights into the molecular signature of the V-SVZ niche.