Astrocyte Reprogramming and Brain Homeostasis

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Nervous System".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 1371

Special Issue Editors


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Guest Editor
Head of Neural Stem Cells and Neuroimaging Group, Department of Neurobiology, Hellenic Pasteur Institute, 11521 Athens, Greece
Interests: direct cell reprogramming; miRNAs; reactive astrocytes; neurovascular unit; neuroinflammation

E-Mail Website
Guest Editor
Neural Stem Cells and Neuroimaging Group, Department of Neurobiology, Hellenic Pasteur Institute, 11521 Athens, Greece
Interests: direct neurogenic reprogramming; miRNAs; neurogenic post-transcriptional mechanisms; neuroinflammation

Special Issue Information

Dear Colleagues,

The latest advances in CNS research have revealed astrocytes to be crucial mediators of both brain homeostasis and disease. Due to their unique intrinsic transcriptional and metabolic properties, astrocytes are being extensively studied as potential therapeutic targets for various CNS diseases, such as neurodegenerative diseases, stroke, and neuroinflammatory conditions.

Consequently, direct astrocytic reprogramming to induced neurons (iNs) takes advantage of the intrinsic neural stem cell potential of brain resident astrocytes to replace degenerating neurons. Over the last few years, astrocytic cell fate conversion to iNs has been well established in vitro and in vivo through employing combinations of transcription factors, miRNAs, or chemical cocktails using astrocytes of different CNS regions. In vivo neurogenic reprogramming, in particular, is still in its early stages, but it holds great promise as a therapeutic option for endogenous neuronal replacement in injured or diseased CNSs.

On the other hand, the unique metabolic properties of astrocytes in supporting neuronal function, such as controlling lipid metabolism and glutamate uptake, have become the focus of recent studies that aim to improve the understanding of the pathologies of neurodegenerative and neuroinflammatory diseases and explore potential therapeutic targets in the context of these diseases.

In this Special Issue, we will aim to present the most recent advances in in vitro and in vivo astrocytic reprogramming, focusing on novel strategies for generating functionally mature neurons, underlying molecular mechanisms, and the characterization of iNs using new technologies such as scRNA-Seq, spatial transcriptomics, and patch-Seq. We will also aim to discuss the progress towards achieving direct in vivo reprogramming in various mouse models of disease and the challenges hindering progress, as well as highlight the most promising approaches for overcoming the major bottlenecks in the field. Overall, we hope to bolster the current knowledge on astrocytic metabolism and its impact on brain homeostasis and showcase the recent advances in astrocytic metabolic reprogramming related to CNS diseases. We welcome the submission of original manuscripts, review articles, and reports on new technologies for the study of astrocytic reprogramming and/or astrocyte function, as well as submissions on the above topics.

Dr. Dimitra Thomaidou
Dr. Elsa Papadimitriou
Guest Editors

Manuscript Submission Information

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Keywords

  • in vitro astrocytic reprogramming
  • in vivo astrocytic reprogramming
  • induced neurons
  • transcription factors
  • miRNAs
  • small molecules
  • direct reprogramming mechanisms
  • scRNA-seq
  • gene regulatory networks
  • astrocytic metabolism
  • metabolic reprogramming

Published Papers (1 paper)

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Research

16 pages, 3950 KiB  
Article
Astrocytes Undergo Metabolic Reprogramming in the Multiple Sclerosis Animal Model
by Sofia Pereira das Neves, João Carlos Sousa, Ricardo Magalhães, Fuying Gao, Giovanni Coppola, Sebatien Mériaux, Fawzi Boumezbeur, Nuno Sousa, João José Cerqueira and Fernanda Marques
Cells 2023, 12(20), 2484; https://doi.org/10.3390/cells12202484 - 19 Oct 2023
Viewed by 1092
Abstract
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that presents a largely unknown etiopathology. The presence of reactive astrocytes in MS lesions has been described for a long time; however, the role that these cells play in the [...] Read more.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that presents a largely unknown etiopathology. The presence of reactive astrocytes in MS lesions has been described for a long time; however, the role that these cells play in the pathophysiology of MS is still not fully understood. Recently, we used an MS animal model to perform high-throughput sequencing of astrocytes’ transcriptome during disease progression. Our data show that astrocytes isolated from the cerebellum (a brain region typically affected in MS) showed a strong alteration in the genes that encode for proteins related to several metabolic pathways. Specifically, we found a significant increase in glycogen degradation, glycolytic, and TCA cycle enzymes. Together with these alterations, we detected an upregulation of genes that characterize “astrocyte reactivity”. Additionally, at each disease time point we also reconstructed the morphology of cerebellum astrocytes in non-induced controls and in EAE animals, near lesion regions and in the normal-appearing white mater (NAWM). We found that near lesions, astrocytes presented increased length and complexity compared to control astrocytes, while no significant alterations were observed in the NAWM. How these metabolic alterations are linked with disease progression is yet to be uncovered. Herein, we bring to the literature the hypothesis of performing metabolic reprogramming as a novel therapeutic approach in MS. Full article
(This article belongs to the Special Issue Astrocyte Reprogramming and Brain Homeostasis)
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