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.

Monitoring in vitro neural stem cell differentiation based on surface-enhanced Raman spectroscopy using a gold nanostar array

2015 ◽  
Vol 3 (16) ◽  
pp. 3848-3859 ◽  
Author(s):  
Waleed Ahmed El-Said ◽  
Seung U. Kim ◽  
Jeong-Woo Choi
Keyword(s):  
Stem Cell ◽  
Neural Stem Cell ◽  
Stem Cell Differentiation ◽  
Surface Enhanced Raman Spectroscopy ◽  
Invasive Monitoring ◽  
Non Invasive ◽  
Cell Chip ◽  
Surface Enhanced ◽  
Surface Enhanced Raman

Neuro-cell chip was developed for non-invasive monitoring of neural stem cell stimulation using SERS technique that enabled the real-time monitoring, which is important for tissue development protocols.

scholarly journals The MAP Kinase Phosphatase MKP-1 Modulates Neurogenesis via Effects on BNIP3 and Autophagy

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1871
Author(s):  
Yinghui Li ◽  
Marc W. Halterman
Keyword(s):  
Stem Cell ◽  
Map Kinase ◽  
Neural Stem Cell ◽  
Neural Plasticity ◽  
Stem Cell Differentiation ◽  
Interacting Protein ◽  
Critical Window ◽  
Map Kinase Phosphatase ◽  
Adenovirus E1b

Inherited and acquired defects in neurogenesis contribute to neurodevelopmental disorders, dysfunctional neural plasticity, and may underlie pathology in a range of neurodegenerative conditions. Mitogen-activated protein kinases (MAPKs) regulate the proliferation, survival, and differentiation of neural stem cells. While the balance between MAPKs and the family of MAPK dual-specificity phosphatases (DUSPs) regulates axon branching and synaptic plasticity, the specific role that DUSPs play in neurogenesis remains unexplored. In the current study, we asked whether the canonical DUSP, MAP Kinase Phosphatase-1 (MKP-1), influences neural stem cell differentiation and the extent to which DUSP-dependent autophagy is operational in this context. Under basal conditions, Mkp-1 knockout mice generated fewer doublecortin (DCX) positive neurons within the dentate gyrus (DG) characterized by the accumulation of LC3 puncta. Analyses of wild-type neural stem cell (NSC) differentiation in vitro revealed increased Mkp-1 mRNA expression during the initial 24-h period. Notably, Mkp-1 KO NSC differentiation produced fewer Tuj1-positive neurons and was associated with increased expression of the BCL2/adenovirus E1B 19-kD protein-interacting protein 3 (BNIP3) and levels of autophagy. Conversely, Bnip3 knockdown in differentiated Mkp-1 KO NSCs reduced levels of autophagy and increased neuronal yields. These results indicate that MKP-1 exerts a pro-neurogenic bias during a critical window in NSC differentiation by regulating BNIP3 and basal autophagy levels.

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 Dynamic Activity of miR-125b and miR-93 during Murine Neural Stem Cell Differentiation In Vitro and in the Subventricular Zone Neurogenic Niche

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e67411 ◽  
Author(s):  
Annalisa Lattanzi ◽  
Bernhard Gentner ◽  
Daniela Corno ◽  
Tiziano Di Tomaso ◽  
Pieter Mestdagh ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Neural Stem Cell ◽  
Subventricular Zone ◽  
Stem Cell Differentiation ◽  
Dynamic Activity ◽  
Neurogenic Niche

scholarly journals Diverse but unique astrocytic phenotypes during embryonic stem cell differentiation, culturing and aging

2021 ◽  
Author(s):  
Kiara Freitag ◽  
Pascale Eede ◽  
Andranik Ivanov ◽  
Shirin Schneeberger ◽  
Tatiana Borodina ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Calcium Signalling ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
The Central Nervous System ◽  
Transcriptomic Level

Astrocytes are resident glia cells of the central nervous system (CNS) that play complex and heterogeneous roles in brain development, homeostasis and disease. Since their vast involvement in health and disease is becoming increasingly recognized, suitable and reliable tools for studying these cells in vivo and in vitro are of utmost importance. One of the key challenges hereby is to adequately mimic their context-dependent in vivo phenotypes and functions in vitro. To better understand the spectrum of astrocytic variations in defined settings we performed a side-by-side-comparison of embryonic stem cell (ESC)-derived astrocytes as well as primary neonatal and adult astrocytes, revealing major differences on a functional and transcriptomic level, specifically on proliferation, migration, calcium signalling and cilium activity. Our results highlight the need to carefully consider the choice of astrocyte origin and phenotype with respect to age, isolation and culture protocols based on the respective biological question.

The characterization of gene expression during mouse neural stem cell differentiation in vitro

2012 ◽  
Vol 506 (1) ◽  
pp. 50-54 ◽  
Author(s):  
Ji Hyun Park ◽  
Mi Ran Choi ◽  
Kyoung Sun Park ◽  
Seung Hyun Kim ◽  
Kyoung Hwa Jung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Neural Stem Cell ◽  
Stem Cell Differentiation

scholarly journals HIF-1α Affects the Neural Stem Cell Differentiation of Human Induced Pluripotent Stem Cells via MFN2-Mediated Wnt/β-Catenin Signaling

2021 ◽  
Vol 9 ◽  
Author(s):  
Peng Cui ◽  
Ping Zhang ◽  
Lin Yuan ◽  
Li Wang ◽  
Xin Guo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Neural Stem Cell ◽  
Pluripotent Stem Cells ◽  
Stem Cell Differentiation ◽  
Differentiation Potential ◽  
Developmental Potential ◽  
Induced Pluripotent

Hypoxia-inducible factor 1α (HIF-1α) plays pivotal roles in maintaining pluripotency, and the developmental potential of pluripotent stem cells (PSCs). However, the mechanisms underlying HIF-1α regulation of neural stem cell (NSC) differentiation of human induced pluripotent stem cells (hiPSCs) remains unclear. In this study, we demonstrated that HIF-1α knockdown significantly inhibits the pluripotency and self-renewal potential of hiPSCs. We further uncovered that the disruption of HIF-1α promotes the NSC differentiation and development potential in vitro and in vivo. Mechanistically, HIF-1α knockdown significantly enhances mitofusin2 (MFN2)-mediated Wnt/β-catenin signaling, and excessive mitochondrial fusion could also promote the NSC differentiation potential of hiPSCs via activating the β-catenin signaling. Additionally, MFN2 significantly reverses the effects of HIF-1α overexpression on the NSC differentiation potential and β-catenin activity of hiPSCs. Furthermore, Wnt/β-catenin signaling inhibition could also reverse the effects of HIF-1α knockdown on the NSC differentiation potential of hiPSCs. This study provided a novel strategy for improving the directed differentiation efficiency of functional NSCs. These findings are important for the development of potential clinical interventions for neurological diseases caused by metabolic disorders.

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