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Natarajan, P. ; Koupourtidou, C. ; de Resseguier, T.* ; Thorwirth, M. ; Bocchi, R. ; Fischer-Sternjak, J. ; Gleiss, S.* ; Rodrigues, D.* ; Myoga, M.H.* ; Ninkovic, J. ; Masserdotti, G. ; Götz, M.

Single cell deletion of the transcription factors Trps1 and Sox9 in astrocytes reveals novel functions in the adult cerebral cortex.

Glia, 22 (2024)

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	Open Access Gold (Paid Option)

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Astrocytes play key roles in brain function, but how these are orchestrated by transcription factors (TFs) in the adult brain and aligned with astrocyte heterogeneity is largely unknown. Here we examined the localization and function of the novel astrocyte TF Trps1 (Transcriptional Repressor GATA Binding 1) and the well-known astrocyte TF Sox9 by Cas9-mediated deletion using Mokola-pseudotyped lentiviral delivery into the adult cerebral cortex. Trps1 and Sox9 levels showed heterogeneity among adult cortical astrocytes, which prompted us to explore the effects of deleting either Sox9 or Trps1 alone or simultaneously at the single-cell (by patch-based single-cell transcriptomics) and tissue levels (by spatial transcriptomics). This revealed TF-specific functions in astrocytes, such as synapse maintenance with the strongest effects on synapse number achieved by Trps1 deletion and a common effect on immune response. In addition, spatial transcriptomics showed non-cell-autonomous effects on the surrounding cells, such as oligodendrocytes and other immune cells with TF-specific differences on the type of immune cells: Trps1 deletion affecting monocytes specifically, while Sox9 deletion acting mostly on microglia and deletion of both TF affecting mostly B cells. Taken together, this study reveals novel roles of Trps1 and Sox9 in adult astrocytes and their communication with other glial and immune cells.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Sox9 ; Trps1 ; Astrocyte Function ; Astrocyte Heterogeneity ; Immune Cells ; Oligodendrocytes ; Reactive Astrocytes; Brain; Expression; Glia

ISSN (print) / ISBN 0894-1491

e-ISSN 1098-1136

Journal Glia

Quellenangaben Pages: 22

Publisher Wiley

Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Stem Cell Research (ISF)

Grants Deutsche Forschungsgemeinschaft