Astrocyte Reprogramming and Brain Homeostasis

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

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