Single Cell Deletion of the Transcription Factors Trps1 and Sox9 in Astrocytes Reveals Novel Functions in the Adult Cerebral Cortex
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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.
SEEK ID: http://lmmeisd-2.srv.mwn.de/studies/134
Projects: SyNergy: Published Datasets
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Created: 23rd May 2025 at 11:00
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Projects: SyNergy: Published Datasets, SyNergy: Unpublished Datasets
Institutions: Helmholtz Munich, LMU
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Projects: SyNergy: Published Datasets, SyNergy: Unpublished Datasets, Test Programme: Project 1
Institutions: LMU Klinikum
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Projects: SyNergy: Published Datasets, SyNergy: Unpublished Datasets
Institutions: Helmholtz Munich
Please visit the 'Related items' tab within the profile page to explore associated studies in more detail.
Neurological diseases are on the rise – and as societies age, they affect an ever-increasing number of people, not only in Europe, but worldwide.
The Munich Cluster for Systems Neurology (SyNergy) investigates how complex neurological diseases such as Alzheimer's disease, stroke, and multiple sclerosis develop. Even though these diseases differ in their clinical manifestations, overlapping mechanisms are involved in their development. For example, the immune system gets activated in dementia, ...
Projects: SyNergy: Published Datasets, SyNergy: Unpublished Datasets
Web page: https://www.synergy-munich.de
This project serves as a centralized repository for omics datasets published by research groups within the SyNergy Cluster. It encompasses investigations such as proteomics and transcriptomics, which are further divided into individual studies led by SyNergy members. Each study is linked to relevant publications, assays and data files (with links to external repositories).
To explore investigations and their associated studies in more detail, please visit the 'Related items' tab on the Project ...
Programme: Munich Cluster for Systems Neurology (SyNergy)
Public web page: Not specified
Submitter: Rainer Malik
Studies: A genome-wide in vivo CRISPR screen identifies essential regulators of T..., Adult neural stem cell activation in mice is regulated by the day/night ..., Diet triggers specific responses of hypothalamic astrocytes in time and ..., Direct neuronal reprogramming of NDUFS4 patient cells identifies the unf..., Distinct molecular profiles of skull bone marrow in health and neurologi..., Early adaptive immune activation detected in monozygotic twins with prod..., Heterogeneity of neurons reprogrammed from spinal cord astrocytes by the..., High-calorie diets uncouple hypothalamic oxytocin neurons from a gut-to-..., Histone Deacetylase 9 Activates IKK to Regulate Atherosclerotic Plaque V..., Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitme..., Innate immune memory after brain injury drives inflammatory cardiac dysf..., MicroRNAs from extracellular vesicles as a signature for Parkinson's dis..., Microglia in white matter aging, Molecular diversity of diencephalic astrocytes reveals adult astrogenesi..., Multiomic ALS signatures highlight subclusters and sex differences sugge..., Multi‐omic landscaping of human midbrains identifies disease‐relevant mo..., Myelin degeneration in leucodystrophies, Neuronal mitochondria transport Pink1 mRNA via synaptojanin 2 to support..., Oligodendrocytes in AD models, Oligodendrocytes in white matter aging, Parkinson's disease motor symptoms rescue by CRISPRa‐reprogramming astro..., Peripheral expression of brain-penetrant progranulin rescues pathologies..., Phagocyte-mediated synapse removal in cortical neuroinflammation is prom..., Shared inflammatory glial cell signature after stab wound injury, reveal..., Single Cell Deletion of the Transcription Factors Trps1 and Sox9 in Astr..., Skin and gut imprinted helper T cell subsets exhibit distinct functional..., Spatial Transcriptomics-correlated Electron Microscopy maps transcriptio..., Spatial centrosome proteome of human neural cells uncovers disease-relev..., T cells modulate the microglial response to brain ischemia, Twin study identifies early immunological and metabolic dysregulation of...
Assays: Expression profiling: Bulk RNA-seq (human), Expression profiling: Bulk RNA-seq (human), Expression profiling: Bulk RNA-seq (human), Expression profiling: Bulk RNA-seq (human) + smallRNA-seq (human), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Bulk RNA-seq (rat), Expression profiling: MERFISH Spatial Transcriptomics (mouse), Expression profiling: Microarray (zebrafish), Expression profiling: RiboTag-mRNA-seq (mouse), Expression profiling: Small RNA-seq (human), Expression profiling: Spatial Transcriptomics (mouse), Expression profiling: Spatial Transcriptomics (mouse), Expression profiling: Spatial Transcriptomics correlated Electron Micros..., Expression profiling: scRNA-seq (human), Expression profiling: scRNA-seq (human), Expression profiling: scRNA-seq (human), Expression profiling: scRNA-seq (human), Expression profiling: scRNA-seq (human), Expression profiling: scRNA-seq (human) (Day 20), Expression profiling: scRNA-seq (human) (Day 5), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse) + Bulk RNA-seq (mouse), Expression profiling: small RNA-seq (human), Expression profiling: small RNA-seq (mouse), Genome binding/occupancy profiling: Bulk ATAC-seq (mouse), Genome binding/occupancy profiling: Bulk ATAC-seq (mouse), Genome binding/occupancy profiling: CUT&Tag sequencing (mouse), Genome binding/occupancy profiling: snATAC-seq (mouse), Genome wide (GW) and validation CRISPR screens (rat)
Submitter: Aditi Methi
Assay type: Transcriptomics
Technology type: Sequencing
Investigation: Transcriptomics (Published)
Submitter: Aditi Methi
Assay type: Transcriptomics
Technology type: Sequencing
Investigation: Transcriptomics (Published)
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 ...
Creators: None
Submitter: Aditi Methi
External LinkAstrocyte-specific lentiviral constructs carrying gRNAs targeting Sox9, Trps1 and or both were injected in the cerebral cortex of adult transgenic mice expressing Cas9 protein. Transduced cells were retrived from the cortex 7 and 21 days post injection and subjected to SmartSeq2 for single cell sequencing
Creators: None
Submitter: Aditi Methi
Abstract (Expand)
Authors: Poornemaa Natarajan, Christina Koupourtidou, Thibault de Resseguier, Manja Thorwirth, Riccardo Bocchi, Judith Fischer-Sternjak, Sarah Gleiss, Diana Rodrigues, Michael H Myoga, Jovica Ninkovic, Giacomo Masserdotti, Magdalena Götz
Date Published: 28th Nov 2024
Publication Type: Journal
