Features of the in vitro expression profile of hippocampal neurogenic niche cells during optogenetic stimulation

2021 ◽  
Vol 67 (1) ◽  
pp. 34-41
Author(s):  
E.D. Khilazheva ◽  
A.V. Morgun ◽  
E.B. Boytsova ◽  
A.I. Mosiagina ◽  
A.N. Shuvaev ◽  
...  

In the central nervous system of mammals, there are specialized areas in which neurogenesis — neurogenic niches — is observed in the postnatal period. It is believed that astrocytes in the composition of neurogenic niches play a significant role in the regulation of neurogenesis, and therefore they are considered as a promising “target” for the possible control of neurogenesis, including the use of optogenetics. In the framework of this work, we formed an in vitro model of a neurogenic niche, consisting of cerebral endothelial cells, astrocytes and neurospheres. Astrocytes in the neurogenic niche model expressed canalorodopsin ChR2 and underwent photoactivation. The effect of photoactivated astrocytes on the expression profile of neurogenic niche cells was evaluated using immunocytochemical analysis methods. It was found that intact astrocytes in the composition of the neurogenic niche contribute to neuronal differentiation of stem cells, as well as the activation of astroglia expressing photosensitive proteins, changes the expression of molecules characterized by intercellular interactions of pools of resting and proliferating cells in the composition of the neurogenic niche with the participation of NAD+ (Cx43, CD38, CD157), lactate (MCT1). In particular, the registered changes reflect a violation of the paracrine intercellular interactions of two subpopulations of cells, one of which acts as a source of NAD+, and the second as a consumer of NAD+ to ensure the processes of intracellular signal transduction; a change in the mechanisms of lactate transport due to aberrant expression of the lactate transporter MCT1 in cells forming a pool of cells developing along the neuronal path of differentiation. In general, with photostimulation of niche astrocytes, the total proliferative activity increases mainly due to neural progenitor cells, but not neural stem cells. Thus, optogenetic activation of astrocytes can become a promising tool for controlling the activity of neurogenesis processes and the formation of a local proneurogenic microenvironment in an in vitro model of a neurogenic niche.

2011 ◽  
Vol 43 (2) ◽  
pp. 91-100 ◽  
Author(s):  
Cornelia Hildebrandt ◽  
Heiko Büth ◽  
Hagen Thielecke

2016 ◽  
Vol 364 (3) ◽  
pp. 573-584 ◽  
Author(s):  
Patrick Wuchter ◽  
Rainer Saffrich ◽  
Stefan Giselbrecht ◽  
Cordula Nies ◽  
Hanna Lorig ◽  
...  

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 758 ◽  
Author(s):  
Ivana Manini ◽  
Maria Elisabetta Ruaro ◽  
Riccardo Sgarra ◽  
Anna Bartolini ◽  
Federica Caponnetto ◽  
...  

Exosomes are one of the most important mediators of the cross talk occurring between glioma stem cells (GSCs) and the surrounding microenvironment. We have previously shown that exosomes released by patient-derived glioma-associated stem cells (GASC) are able to increase, in vitro, the aggressiveness of both GSC and glioblastoma cell lines. To understand which molecules are responsible for this tumour-supporting function, we performed a descriptive proteomic analysis of GASC-exosomes and identified, among the others, Semaphorin7A (SEMA7A). SEMA7A was described as a promigratory cue in physiological and pathological conditions, and we hypothesised that it could modulate GSC migratory properties. Here, we described that SEMA7A is exposed on GASC-exosomes’ surface and signals to GSC through Integrin β1. This interaction activates focal adhesion kinase into GSC and increases their motility, in our patient-based in vitro model. Our findings suggest SEMA7A-β1-integrin as a new target to disrupt the communication between GSCs and the supporting microenvironment.


Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1087 ◽  
Author(s):  
Bonafede ◽  
Brandi ◽  
Manfredi ◽  
Scambi ◽  
Schiaffino ◽  
...  

Stem cell therapy represents a promising approach in the treatment of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). The beneficial effect of stem cells is exerted by paracrine mediators, as exosomes, suggesting a possible potential use of these extracellular vesicles as non-cell based therapy. We demonstrated that exosomes isolated from adipose stem cells (ASC) display a neuroprotective role in an in vitro model of ALS. Moreover, the internalization of ASC-exosomes by the cells was shown and the molecules and the mechanisms by which exosomes could exert their beneficial effect were addressed. We performed for the first time a comprehensive proteomic analysis of exosomes derived from murine ASC. We identified a total of 189 proteins and the shotgun proteomics analysis revealed that the exosomal proteins are mainly involved in cell adhesion and negative regulation of the apoptotic process. We correlated the protein content to the anti-apoptotic effect of exosomes observing a downregulation of pro-apoptotic proteins Bax and cleaved caspase-3 and upregulation of anti-apoptotic protein Bcl-2 α, in an in vitro model of ALS after cell treatment with exosomes. Overall, this study shows the neuroprotective effect of ASC-exosomes after their internalization and their global protein profile, that could be useful to understand how exosomes act, demonstrating that they can be employed as therapy in neurodegenerative diseases.


PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e78226 ◽  
Author(s):  
Katja Kriebel ◽  
Anne Biedermann ◽  
Bernd Kreikemeyer ◽  
Hermann Lang

Stem Cells ◽  
1996 ◽  
Vol 14 (S1) ◽  
pp. 194-199 ◽  
Author(s):  
Georges Uzan ◽  
Marie‐Hélène Prandini ◽  
Jean‐Philippe Rosa ◽  
Rolande Berthier

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