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Single cell deletion of the transcription factors Sox9 and Trps1 reveals novel functions in adult cortical astrocytes [RNA-seq]

ABSTRACT: Purpose of the study is to evaluate the impact of Sox9 and Trps1 knock-down in vivo at single cell level

ORGANISM(S): Mus musculus

PROVIDER: GSE279677 | GEO | 2025/02/10

REPOSITORIES: GEO

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

Project description: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.

2025-02-10 | GSE279676 | GEO

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

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

| PRJNA1174069 | ENA

Single cell deletion of the transcription factors Sox9 and Trps1 reveals novel functions in adult cortical astrocytes [RNA-seq]

Project description:Single cell deletion of the transcription factors Sox9 and Trps1 reveals novel functions in adult cortical astrocytes [RNA-seq]

| PRJNA1174066 | ENA

Single Cell Deletion of the Transcription Factors Trps1 and Sox9 in Astrocytes Reveals Novel Functions in the Adult Cerebral Cortex.

Project description: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.

| S-EPMC11845849 | biostudies-literature

Transcriptional targets of Trps1 in vibrissae

Project description:Mutations in TRPS1 cause trichorhinophalangeal syndrome types I and III, which are characterized by sparse scalp hair in addition to craniofacial and skeletal abnormalities. Trps1 is a vertebrate transcription factor containing nine zinc-finger domains, including a GATA-type zinc finger through which it binds DNA. Mice in which the GATA domain of Trps1 has been deleted (Trps1∆gt/∆gt) have a reduced number of pelage follicles and lack vibrissae follicles postnatally. To identify the transcriptional targets of Trps1 in the developing vibrissa follicle, we performed microarray hybridization analysis comparing expression patterns in the whisker pads of wild-type versus Trps1∆gt/∆gt embryos. We identified a number of transcription factors and Wnt inhibitors among transcripts downregulated in the mutant embryos, and several extracellular matrix proteins there were upregulated in the mutant samples. Whole whisker pads were dissected from E12.5 embryos and total RNA was isolated using the RNeasy Mini Kit (Qiagen). Triplicate RNA samples from three independent embryos of each genotype were amplified and labeled for hybridization to Affymetrix GeneChip MOE430A microarrays using Affymetrix reagents and protocols. The data output was analyzed using GeneSpring GX 10.0 commercial software (Agilent Technologies). P-values were calculated using an unpaired t-test. Expression values with a p-value less than or equal to 0.05 and a fold difference of at least 1.5 relative to wild-type baseline expression levels were considered significant.

2011-12-22 | E-GEOD-33766 | biostudies-arrayexpress

Olfactory bulb gene expression profiling upon loss of Sox9 in adult astrocytes

Project description:The goal of this study is to determine how the loss of the transcription factor Sox9 affects the molecular profiles of adult astrocytes from the olfactory. We performed RNA-sequencing on wildtype and Sox9 knockout (KO) astrocytes from the olfactory bulb and analyzed the molecular signatures of Sox9 KO astrocytes compared to the wildtype control.

2021-07-28 | GSE180841 | GEO

Transcriptome profiling of radiation-transformed breast cells after TRPS1 siRNA knockdown.

Project description:TRPS1 was recently identified as a radiation marker in breast cancer. In order to characterise the molecular phenotype that is associated with TRPS1 we knocked out the gene in two radiation-transformed breast cell lines.

2017-10-01 | E-MTAB-6008 | biostudies-arrayexpress

Transcriptional targets of Trps1 in vibrissae

2011-12-22 | GSE33766 | GEO

TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells

Project description:Yes-associated protein (YAP), the downstream transducer of the Hippo pathway is a key regulator of organ size, differentiation and tumourigenesis. Yet, the activity of YAP can also be modulated by Hippo-independent functions. To disclose these Hippo-independent regulators, we performed a genome-wide CRISPR screening approach that identified the transcriptional repressor protein Trichorhinophalangeal Syndrome 1 (TRPS1) as a potent repressor of YAP-dependent transactivation. Using RNA-Sequencing and ChIP-Sequencing approaches we show that TRPS1 globally regulates YAP-dependent transcription by binding to a large set of joint genomic sites, mainly enhancers. Mechanistically, TRPS1 represses YAP-dependent enhancers function by recruiting a spectrum of corepressor complexes to joint sites. Consequently, loss of TRPS1 leads to activation of enhancers due to increased H3K27 acetylation and an altered promoter-enhancer interaction landscape. TRPS1 is commonly amplified in breast cancer which is associated decreased YAP activity and leads to a decreased frequency of intratumoural immune cells. Consistently, depletion of TRPS1 in the syngeneic 4T1 tumour model leads to a strongly decreased tumour growth in vivo. Our study uncovers TRPS1 as a new epigenetic regulator of YAP activity and it connects repression of YAP-dependent enhancer function to breast cancer. For project-related queries, please contact bjoern.voneyss@leibniz-fli.de <mailto:bjoern.voneyss@leibniz-fli.de>.

2018-08-09 | PXD009819 | Pride

TRPS1 impairs myogenic differentiation in embryonal rhabdomyosarcoma [ChIP-seq]

Project description:We report here the analysis of TRPS1 chromatin binding by ChIP-Seq in embryonal rhabdomyosarcoma RD cells. We use here parental and TRPS1-KO RD cells. RD cells and RD-TRPS1-KO cells were cultured in growth medium and chromatin was prepared. TRPS1 DNA binding in RD cells and RD-TRPS1-KO cells using a selfmade antibody (referenced in Elster et al.) was determined by ChIP-seq.

2023-07-24 | GSE197550 | GEO

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