Recent research, published in the journal ‘Cell Reports‘, revealed that as mammals age, their sense of smell deteriorates.
Adult murine neural stem cells (NSCs) produce neurons in drastically deteriorating numbers with age. Researchers have now studied why this is the case.
The research was conducted at Helmholtz Zentrum München and the University Medical Centre Mainz. For their research, the scientists tracked the growth of stem cells in the brains of mice using what are known as confetti reporters. Then they examined the complex data which was obtained by using intelligent algorithms.
In mammals, production of new neurons (neurogenesis) is chiefly limited to early childhood. It occurs in adulthood only in some regions of the forebrain. Olfactory neurons are one of such exceptions, which generate from stem cells by several intermediate stages.
“The generation of these neurons reduces with advancing age. In our new research we wanted to discover the cellular basis and role of stem cells in the process,” says Dr. Carsten Marr. He is a research team leader at the Institute of Computational Biology (ICB) of Helmholtz Zentrum München.
An interdisciplinary team of experts from the Helmholtz Zentrum München was formed to shed light on this question. “Our approach utilized what are identified as confetti reporters for lineage tracing.
Outcomes of the study
In mouse brains, individual stem cells and all their descendants (called clones) were induced to light up in a specific color”, says Filippo Calzolari. Thus, over time the scientists could distinguish clones by using different colors which give the technique its name.
“In the next step, clones found in young and older mice were compared to find out the contribution of individual stem cells and intermediates make to the neurogenesis of mature olfactory cells”, Calzolari adds.
However, systematic analysis of the images proved almost impossible for humans, because the available data were heterogeneous. It made the comparison of young and old brains difficult. Here the expertise of Carsten Marr and his colleagues came into play.
They are experts in the quantification of single-cell dynamics, i.e. the study of how many and which cells of a large population make which cell fate decisions.
For this, scientists use artificial intelligence approaches, develop mathematical models and deduce algorithms to analyze the image data.
“We related the confetti measurements with some mathematical models of neurogenesis,” explains Lisa Bast. “We found that the cells ability of self-renewal deteriorates in old age, particularly in confident intermediate stages called transit amplifying progenitors.”
Also, the investigation exposed that asymmetric cell division and stem cells dormancy increased in older mice. “Thus, it indicates that in old age, rarer cells differentiate into olfactory cells. As they tend to stay in the stem cell pool and become less active. So, the production comes to a stop”, says Jovica Ninkovic.
This is the first work in which researchers could quantitatively describe the neural stem cells behavior in the living mammalian brain using a mathematical model.