scholarly journals Subtle Changes in Clonal Dynamics Underlie the Age-Related Decline in Neurogenesis

2017 ◽  
Author(s):  
Lisa Bast ◽  
Filippo Calzolari ◽  
Michael Strasser ◽  
Jan Hasenauer ◽  
Fabian Theis ◽  
...  
Keyword(s):  
Stem Cell ◽  
Neural Stem Cell ◽  
Population Data ◽  
Stem Cell Differentiation ◽  
Adult Neural Stem Cell ◽  
Adult Mice ◽  
Age Related ◽  
Stem Cell Divisions ◽  
Underlying Mechanisms ◽  
Middle Aged Adult

SUMMARYNeural stem cells in the adult murine brain have only a limited capacity to self-renew, and the number of neurons they generate drastically declines with age. How cellular dynamics sustain neurogenesis and how alterations with age may result in this decline, are both unresolved issues. Therefore, we clonally traced neural stem cell lineages using confetti reporters in young and middle-aged adult mice. To understand underlying mechanisms, we derived mathematical population models of adult neurogenesis that explain the observed clonal cell type abundances. Models fitting the data best consistently show self renewal of transit amplifying progenitors and rapid neuroblast cell cycle exit. Most importantly, we identified an increase of asymmetric stem cell divisions at the expense of symmetric stem cell differentiation with age. Beyond explaining existing longitudinal population data, our model identifies a particular cellular strategy underlying adult neural stem cell homeostasis that gives insights into the aging of a stem cell compartment.

scholarly journals Neural Stem Cell-Derived Exosomes Regulate Neural Stem Cell Differentiation Through miR-9-Hes1 Axis

2021 ◽  
Vol 9 ◽  
Author(s):  
Ping Yuan ◽  
Lu Ding ◽  
Huili Chen ◽  
Yi Wang ◽  
Chunhong Li ◽  
...  
Keyword(s):  
Stem Cell ◽  
Neural Stem Cell ◽  
Stem Cell Differentiation ◽  
Bioactive Molecules ◽  
Downstream Target ◽  
Positive Effects ◽  
Primary Mouse ◽  
The Central Nervous System ◽  
Underlying Mechanisms

Exosomes, a key element of the central nervous system microenvironment, mediate intercellular communication via horizontally transferring bioactive molecules. Emerging evidence has implicated exosomes in the regulation of neurogenesis. Recently, we compared the neurogenic potential of exosomes released from primary mouse embryonic neural stem cells (NSCs) and astrocyte-reprogrammed NSCs, and observed diverse neurogenic potential of those two exosome populations in vitro. However, the roles of NSC-derived exosomes on NSC differentiation and the underlying mechanisms remain largely unknown. In this study, we firstly demonstrated that NSC-derived exosomes facilitate the differentiation of NSCs and the maturation of both neuronal and glial cells in defined conditions. We then identified miR-9, a pro-neural miRNA, as the most abundantly expressed miRNA in NSC-derived exosomes. The silencing of miR-9 in exosomes abrogates the positive effects of NSC-derived exosomes on the differentiation of NSCs. We further identified Hes1 as miR-9 downstream target, as the transfection of Hes1 siRNA restored the differentiation promoting potential of NSC-derived exosomes after knocking down exosomal miR-9. Thus, our data indicate that NSC-derived exosomes facilitate the differentiation of NSCs via transferring miR-9, which sheds light on the development of cell-free therapeutic strategies for treating neurodegeneration.

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