Investigation of age-related changes in neuroblast populations using RNA velocity
(2023) BINP52 20212Degree Projects in Bioinformatics
- Abstract
- Adult neurogenesis is the process of generating new neurons from neural stem cells (NSCs) in the adult mammalian brain, which occurs in two neurogenic niches; the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dental gyrus (DG). In rodents, neurogenesis continues throughout life, but this process decreases with age, which may result in cognitive decline. However, it is still poorly understood how aging affects the cell differentiation process throughout neurogenesis. Here, we used scRNA-seq transcriptomics together with RNA velocity analyses to explore differentiation patterns between the diverse populations of cells and follow the neurogenesis continuum with age. We compared... (More)
- Adult neurogenesis is the process of generating new neurons from neural stem cells (NSCs) in the adult mammalian brain, which occurs in two neurogenic niches; the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dental gyrus (DG). In rodents, neurogenesis continues throughout life, but this process decreases with age, which may result in cognitive decline. However, it is still poorly understood how aging affects the cell differentiation process throughout neurogenesis. Here, we used scRNA-seq transcriptomics together with RNA velocity analyses to explore differentiation patterns between the diverse populations of cells and follow the neurogenesis continuum with age. We compared transcriptomes of neuroblasts from three age groups (young, adult, and aged). We revealed that age affects differentiation trajectory at the transcription level, as we found a reverse differentiation movement from neurons to neuroblasts in our velocity maps. Furthermore, we showed that young and adult groups follow a similar differentiation direction from neuroblasts to neurons. We also noticed the upregulation of inflammatory genes in the neuroblast cluster of older groups of mice. Overall, our data advanced our understanding of the aging signature of newly born neuroblasts and raised a hypothesis about cell de-differentiation in aged SVZ. Further investigations with a focus on putative dedifferentiation in aged neuroblasts are therefore warranted. (Less)
- Popular Abstract
- Navigating the aging brain, a journey with the cell’s internal compass
Our fantastic brain can produce new nerve cells throughout life. The formation of new nerve cells helps us learn and form new memories. New nerve cells are born from a particular type of cell called neural stem cells. Neural stem cells are unspecialized cells that can divide and go through several stages before becoming mature nerve cells. But, like almost everything, this capability decreases with age. Understanding these changes can help us develop ways to maintain brain health and improve quality of life as we age. In this study, we have made some progress by examining the role of neuroblasts, a cell type involved in creating new nerve cells in the brain.
New... (More) - Navigating the aging brain, a journey with the cell’s internal compass
Our fantastic brain can produce new nerve cells throughout life. The formation of new nerve cells helps us learn and form new memories. New nerve cells are born from a particular type of cell called neural stem cells. Neural stem cells are unspecialized cells that can divide and go through several stages before becoming mature nerve cells. But, like almost everything, this capability decreases with age. Understanding these changes can help us develop ways to maintain brain health and improve quality of life as we age. In this study, we have made some progress by examining the role of neuroblasts, a cell type involved in creating new nerve cells in the brain.
New nerve cell formation occurs in two specific regions where stem cells are present in adults. These stem cells possess the exceptional capability to replicate themselves and differentiate into other specialized cells, such as nerve cells. There are several stages, from being a stem cell to becoming a mature nerve cell. In this study, we focused on one of these stages called Neuroblast. At this point, the neuroblast possesses the capability to migrate. They can then migrate and relocate from their origin to the region where they will transform into a new nerve cell. We focused on the direction and speed of cell movements to observe how these stages are affected by aging among all the individual cells in our samples.
What is the approach for investigating neuroblasts in aging?
To understand the formation of new brain cells in aging, we have conducted studies on mice, which display similar brain cell characteristics to humans. The mice were separated into three age groups, representing young, adults, and aged individuals. Neuroblasts were isolated from each group, and the gene expression in these cells was analyzed.
In this study, we compared changes in gene expression over time between all age groups of different regions in mice brains. This method is similar to an internal compass in the cell that gives us a general idea of the cell's developmental direction and future state of each cell. We observed that some of the neuroblasts in aged groups changed in a way which gave rise to inflammatory cells. We also observed the reverse direction from nerve cells to neuroblasts in the old mice. Our result raises the hypothesis of cell dedifferentiation, which means the cell grows in reverse, from specialized cells such as nerve cells back to neuroblasts.
Our findings are significant in that they enhance our knowledge of how aging affects the brain and its impact on nerve cell formation. This brings us closer to creating a treatment to address the effects of aging on the brain.
Master’s Degree Project in Bioinformatics 60 credits 2022
Department of Biology, Lund University
Advisors: Henrik Ahlenius and Jonas Fritze
Stem Cell Aging and Neurodegeneration Lab, Lund Stem Cell Center (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9112911
- author
- Torbati, Mostafa
- supervisor
-
- Henrik Ahlenius LU
- Jonas Fritze LU
- organization
- course
- BINP52 20212
- year
- 2023
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9112911
- date added to LUP
- 2023-03-27 13:47:06
- date last changed
- 2023-03-27 13:47:06
@misc{9112911,
abstract = {{Adult neurogenesis is the process of generating new neurons from neural stem cells (NSCs) in the adult mammalian brain, which occurs in two neurogenic niches; the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dental gyrus (DG). In rodents, neurogenesis continues throughout life, but this process decreases with age, which may result in cognitive decline. However, it is still poorly understood how aging affects the cell differentiation process throughout neurogenesis. Here, we used scRNA-seq transcriptomics together with RNA velocity analyses to explore differentiation patterns between the diverse populations of cells and follow the neurogenesis continuum with age. We compared transcriptomes of neuroblasts from three age groups (young, adult, and aged). We revealed that age affects differentiation trajectory at the transcription level, as we found a reverse differentiation movement from neurons to neuroblasts in our velocity maps. Furthermore, we showed that young and adult groups follow a similar differentiation direction from neuroblasts to neurons. We also noticed the upregulation of inflammatory genes in the neuroblast cluster of older groups of mice. Overall, our data advanced our understanding of the aging signature of newly born neuroblasts and raised a hypothesis about cell de-differentiation in aged SVZ. Further investigations with a focus on putative dedifferentiation in aged neuroblasts are therefore warranted.}},
author = {{Torbati, Mostafa}},
language = {{eng}},
note = {{Student Paper}},
title = {{Investigation of age-related changes in neuroblast populations using RNA velocity}},
year = {{2023}},
}