JunB defines functional and structural integrity of the epidermo-pilosebaceous unit in the skin
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA453610 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7065392.fastq.gz | Fastqsanger.gz | |||
| SRR7065393.fastq.gz | Fastqsanger.gz | |||
| SRR7065394.fastq.gz | Fastqsanger.gz | |||
| SRR7065395.fastq.gz | Fastqsanger.gz | |||
| SRR7065396.fastq.gz | Fastqsanger.gz |
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Project description:Here we identified JunB, a member of the AP-1 transcription factor family, regulated epidermal stem cells and sebaceous glands through balancing proliferation and differentiation of progenitors and by suppressing lineage infidelity.
2018-04-26 | GSE113688 | GEO
Project description:Transcription factors ensure skin homeostasis via tight regulation of distinct resident stem cells. Here we report that JunB, a member of the AP-1 transcription factor family, regulates epidermal stem cells and sebaceous glands through balancing proliferation and differentiation of progenitors and by suppressing lineage infidelity. JunB deficiency in basal progenitors results in a dermatitis-like syndrome resembling seborrheic dermatitis harboring structurally and functionally impaired sebaceous glands with a globally altered lipid profile. A fate switch occurs in a subset of JunB deficient epidermal progenitors during wound healing resulting in de novo formation of sebaceous glands. Dysregulated Notch signaling is identified to be causal for this phenotype. In fact, pharmacological inhibition of Notch signaling can efficiently restore the lineage drift, impaired epidermal differentiation and disrupted barrier function in JunB conditional knockout mice. These findings define an unprecedented role for JunB in epidermal-pilosebaceous stem cell homeostasis and its pathology.
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Project description:Fibroblasts residing in the connective tissue of all organs constitute the stem cell niche particularly in connective tissue rich organs like skin. Though the impact of the connective tissue resident fibroblasts on stem cell niches and organ aging is an emerging concept, the underlying mechanisms are largely unresolved. Here, we report a novel mechanism of redox-dependent activation of the transcription factor JunB, which through concomitant upregulation of cyclin dependent kinase inhibitor p16INK4A and repression of IGF-1 dependent cell growth and protein translation initiates the installment of irreversible fibroblast senescence. Fibroblast senescence in turn profoundly disrupts the metabolic and structural niche and its essential interactions with different stem cells thus enforcing depletion of stem cells pools and skin tissue decline. In fact, silencing of JunB in a fibroblast niche-specific knock out mouse - by the reinstatement of IGF-1 and p16 levels - fully restored skin stem cell pools and overall tissue integrity of the skin. We here uncovered a previously unreported role of JunB in the control of the endogenous connective tissue niche and identified promising targets to combat skin aging and associated pathologies.
2021-07-16 | GSE180008 | GEO
Project description:Single cell RNAseq of human nail unit defines RSPO4 onychofibroblasts and SPINK6 nail epithelium
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Project description:This study is designed to determine the direct target genes of JunB transcription factor in human keratinocytes Mice with epidermal deletion of JunB transcription factor displayed a psoriasis-like inflammation. The relevance of these findings to humans and the mechanisms mediating JunB function are not fully understood. Here, we demonstrate that impaired JunB function via gene silencing or overexpression of a dominant negative mutant increased human keratinocyte cell proliferation but decreased cell barrier function. RNA-seq revealed over 500 genes affected by JunB loss-of-function which included an upregulation of an array of proinflammatory molecules relevant to psoriasis. Among these were TNFa, CCL2, CXCL10, IL6R and SQSTM1, an adaptor protein involved in NF-kB activation. ChIP-Seq and gene reporter analyses showed that JunB directly suppressed SQSTM1 through binding to a consensus AP-1 cis-element located around 2 Kb upstream of SQSTM1-trasncription start site. Similar to JunB loss-of-function, SQSTM1-overexpression induced TNFa, CCL2 and CXCL10. Conversely, NF-kB-inhibition genetically with a mutant IkBa or pharmacologically with PDTC prevented cytokine, but not IL6R, induction by JunB-deficiency. Taken together, our findings indicate that JunB controls epidermal growth, barrier formation and proinflammatory responses through direct and indirect mechanisms, pinpointing SQSTM1 as a key mediator of JunB-suppression of NF-kB-dependent inflammation.
2015-10-05 | GSE63080 | GEO
Project description:Genome-wide mapping of JUNB binding sites in U2OS cell line by ChIP-seq.
2022-09-29 | GSE195991 | GEO
Project description:To determne JunB target gene in human keratincoytes Mice with epidermal deletion of JunB transcription factor displayed a psoriasis-like inflammation. The relevance of these findings to humans and the mechanisms mediating JunB function are not fully understood. Here, we demonstrate that impaired JunB function via gene silencing or overexpression of a dominant negative mutant increased human keratinocyte cell proliferation but decreased cell barrier function. RNA-seq revealed over 500 genes affected by JunB loss-of-function which included an upregulation of an array of proinflammatory molecules relevant to psoriasis. Among these were TNFa, CCL2, CXCL10, IL6R and SQSTM1, an adaptor protein involved in NF-kB activation. ChIP-Seq and gene reporter analyses showed that JunB directly suppressed SQSTM1 through binding to a consensus AP-1 cis-element located around 2 Kb upstream of SQSTM1-trasncription start site. Similar to JunB loss-of-function, SQSTM1-overexpression induced TNFa, CCL2 and CXCL10. Conversely, NF-kB-inhibition genetically with a mutant IkBa or pharmacologically with PDTC prevented cytokine, but not IL6R, induction by JunB-deficiency. Taken together, our findings indicate that JunB controls epidermal growth, barrier formation and proinflammatory responses through direct and indirect mechanisms, pinpointing SQSTM1 as a key mediator of JunB-suppression of NF-kB-dependent inflammation.
2015-10-05 | GSE63079 | GEO
Project description:The AP-1 transcription factor subunit Junb acts as a context-dependent transcriptional regulator. While positive regulatory functions of Junb are widely studied, the mechanism by which Junb exerts negative regulatory functions remains unclear. miRNAs could translate repressor functions of Junb. Therefore, the aim of this study was to identify Junb-dependent miRNAs in immortalized fibroblasts (MEFs) derived from murine Junb knock-out and wildtype embryos. Cells were published previously in Licht et al. (2010) J Clin Invest. 120(7):2307-18.
2015-10-13 | GSE43380 | GEO