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Single cell deletion of the transcription factors Sox9 and Trps1 reveals novel functions in adult cortical astrocytes [Spatial transcriptomics]

ABSTRACT: Astrocytes play key roles in brain function but it is still poorly understood how these are orchestrated by pan-astrocyte transcriptions factors (TFs). Here we examined the function of the well-known pan-astrocyte TF Sox9 and the novel astrocyte TF Trps1 (Transcriptional Repressor GATA Binding 1) by Cas9-mediated in vivo deletion using Mokola-pseudotyped lentiviral delivery into the adult cerebral cortex. The consequences of deleting either Sox9 or Trps1 alone or simultaneously were explored at single cell level (by patch-based single cell transcriptomics) and tissue level (by spatial transcriptomics). This revealed TF-specific functions in astrocytes, like synapse maintenance and immune response, as well as non-cell-autonomous effects on the surrounding cells such as on oligodendrocytes and other immune cells. Interestingly, deleting both factors cancels out some effects, suggesting that they antagonize each other’s function to some extent. Taken together, this study reveals a novel role of Trps1 and Sox9 in adult astrocytes and their communication with other glial and immune cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE279676 | GEO | 2025/02/10

REPOSITORIES: GEO

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Project description:MartínJiménez2017 - Genome-scale reconstruction of the human astrocyte metabolic network This model is described in the article: Genome-Scale Reconstruction of the Human Astrocyte Metabolic Network. Martín-Jiménez CA, Salazar-Barreto D, Barreto GE, González J. Front Aging Neurosci 2017; 9: 23 Abstract: Astrocytes are the most abundant cells of the central nervous system; they have a predominant role in maintaining brain metabolism. In this sense, abnormal metabolic states have been found in different neuropathological diseases. Determination of metabolic states of astrocytes is difficult to model using current experimental approaches given the high number of reactions and metabolites present. Thus, genome-scale metabolic networks derived from transcriptomic data can be used as a framework to elucidate how astrocytes modulate human brain metabolic states during normal conditions and in neurodegenerative diseases. We performed a Genome-Scale Reconstruction of the Human Astrocyte Metabolic Network with the purpose of elucidating a significant portion of the metabolic map of the astrocyte. This is the first global high-quality, manually curated metabolic reconstruction network of a human astrocyte. It includes 5,007 metabolites and 5,659 reactions distributed among 8 cell compartments, (extracellular, cytoplasm, mitochondria, endoplasmic reticle, Golgi apparatus, lysosome, peroxisome and nucleus). Using the reconstructed network, the metabolic capabilities of human astrocytes were calculated and compared both in normal and ischemic conditions. We identified reactions activated in these two states, which can be useful for understanding the astrocytic pathways that are affected during brain disease. Additionally, we also showed that the obtained flux distributions in the model, are in accordance with literature-based findings. Up to date, this is the most complete representation of the human astrocyte in terms of inclusion of genes, proteins, reactions and metabolic pathways, being a useful guide for in-silico analysis of several metabolic behaviors of the astrocyte during normal and pathologic states. This model is hosted on BioModels Database and identified by: MODEL1608180000. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Single cell deletion of the transcription factors Sox9 and Trps1 reveals novel functions in adult cortical astrocytes [Spatial transcriptomics]

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