SERPINA3- a novel keratinocyte differentiation promotor mediates epidermal barrier repair response in psoriatic lesion
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE102000 | GEO | 2017/07/29
SECONDARY ACCESSION(S): PRJNA396168
REPOSITORIES: GEO
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Project description:Purpose:To gain a deeper insight into how Serpina3 regulates neurogenesis and further controling cortex folding in mice brain, RNA-sequencing (RNA-seq) was performed to analyze the genome-wide changes by TCF20 deletion at E15. Methods: Total RNA was extracted from E15 telencephalic tissue of WT and serpina3 cKI mice. Then total RNA was quality controlled and quantified using an Agilent 2100 Bioanalyzer. After converting to cDNA and building library, high-throughput sequencing was performed using the Illumina HiSeq 2500 platform in Annoroad Genomics. Results: Approximately approximately one thousand transcripts showed differential expression between the WT and Serpina3 knock-in brain cortex, with a fold change ≥1.5 and p value <0.05. Gene ontology (GO) analysis showed that the up-regulated genes were enriched in the terms related to neurogenesis, neuronal specification, neural differentiation and secretion by cells. Up-regulated genes showed a significant enrichment of terms involved in up regulation of hypersensitivity and down regulation of inflammatory response. These results reflected the importance of serpina3 in cortical neurogenesis and cortex folding. Conclusions: We conclude that RNA-seq based transcriptome characterization would provide a framework for understanding how serpina3 contribute to brain cortical development.
2021-01-23 | GSE165345 | GEO
Project description:Purpose: To better understand how Serpina3 modulate cortex enpansion and folding. We performed single cell sequencing to reveal the change of cell types in single cell level. Method: Single cell isolation was prepared from P0 telencephalic tissue of wild-type (WT) and serpina3f/+;Nestin-Cre mice. The fragmented cDNAs containing barcode and UMI sequences was built the library. Agilent 2100 Bioanalyzer was used to quality controlled and quantified. Single cell RNA-sequencing analysis was used by the Illumina platform in Annoroad Genomics. Results: Clustering and labeling of these cells visualized on a t-SNE plot between the wild-type (WT) and Serpina3f/+;Nestin-Cre mice brain cortex. Specific layer neurons were increased in Serpina3 knock in mice. Conclusions: Single cell RNA-seq data would provide an overall understanding how SERPINA3 gene contribute to generation of cortical expansion and folding in mice.
2021-01-26 | GSE165440 | GEO
Project description:Human serpina3 modulates cortex expansion and folding
| PRJNA694137 | ENA
Project description:One of the most challenging aspects in multiple sclerosis (MS) research is to understand the mechanisms leading to neurodegeneration and subsequent tissue repair. Here, we aimed to identify biomarkers associated with the progressive phases of the disease that may have neuroprotective potential. To achieve this, we performed a bioinformatic approach integrating transcriptional and proteomic profiles obtained during the course of experimental autoimmune encephalomyelitis (EAE) combined with gene expression microarray data from neuronal differentiation. Integrative analysis of omics data identified two molecules, serine (or cysteine) peptidase inhibitor, clade A, member 3N (Serpina3n) and S100 calcium binding protein A4 (S100A4), as biomarkers up-regulated in chronic progressive EAE whose expression was also induced during neuronal differentiation. Immunofluorescence studies revealed a primarily neuronal expression of Serpina3n and S100A4 during EAE as reflected by their co-localization with β-III-Tubulin in neurons from cerebellum, hippocampus and spinal cord tissues during EAE. Finally, levels of SERPINA3, the human ortholog of murine Serpina3n also known as α1-antichymotrypsin, and S100A4 were increased in cerebrospinal fluid of MS patients compared with non-inflammatory neurological controls. However, only SERPINA3 showed differences across MS clinical forms and levels were significantly elevated in patients with progressive forms of the disease, particularly in patients with primary progressive MS, compared with relapsing-remitting MS and neurological controls. Altogether, these results point to a role of SERPINA3 as biomarker associated with the progressive forms of MS that may also have neuroregenerative potential
2021-02-01 | PXD018173 | Pride
Project description:In cervical cancer, an important mechanism by which tumour cells escape immune surveillance is loss of HLA class I, enabling tumours to evade recognition and lysis by cytotoxic T lymphocytes. Some tumours, however, escape from immune surveillance without accumulating defects in antigen presentation. We hypothesized that tumours with no or partial loss of HLA class I develop alternative mechanisms to prevent immune surveillance. To investigate this hypothesis, genome-wide expression profiling using Illumina arrays was performed on cervical squamous cell carcinomas showing overall loss of HLA class I, partial and normal HLA class I protein expression. Statistical analyses revealed no significant differences in gene expression between tumours with partial (n = 11) and normal HLA class I expression (n = 10). Comparison of tumours with normal/partial HLA class I expression (n = 21) with those with overall loss of HLA class I expression (n = 11) identified 150 differentially expressed genes. Most of these genes were involved in the defense response (n = 27), and, in particular, inflammatory and acute phase responses. Especially SerpinA1 and SerpinA3 were found to be upregulated in HLA positive tumours (3.6 and 8.2 fold, respectively), and this was confirmed by real-time PCR and immunohistochemistry. In a group of 117 tumours, high SerpinA1 and SerpinA3 expression in association with normal/partial HLA expression correlated significantly with poor overall survival (p = 0.035 and p = 0.05, respectively). This study shows that HLA positive tumours are characterized by a higher expression of genes associated with an inflammatory profile and that expression of the acute phase proteins SerpinA1 and SerpinA3 in HLA positive tumours is associated with worse prognosis. Keywords: Cell type comparison
2008-05-23 | GSE10372 | GEO
Project description:Serpina3 modulates neuronal cell fate determination (scRNA sequencing)
| PRJNA694621 | ENA
Project description:Keratinocyte cancers (KC) are the most prevalent malignancies in fair-skinned populations, posing a significant medical and economic burden to health systems. KC originate in the epidermis and mainly comprise basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Here, we combined single-cell transcriptomics, methylomics and multi-omics to investigate the epigenomic dynamics during epidermal differentiation. We identified ~4,000 differentially accessible regions between undifferentiated and differentiated keratinocytes, corresponding to regulatory regions associated with key transcription factors. DNA methylation at these regions defined AK/cSCC subtypes with epidermal stem cell- or keratinocyte-like features. Using cell type deconvolution tools and integration of bulk and single-cell methylomes, we demonstrate that these subclasses are consistent with distinct cells-of-origin. Further characterization of the subclasses with an epigenetic mitotic-like clock, and the study of other unstratified KC entities uncovered distinct phenotypic and clinical features for the subclasses, linking invasive and metastatic KC cases with undifferentiated cells-of-origin. Our study provides a thorough characterization of the epigenomic dynamics underlying human keratinocyte differentiation and uncovers novel links between KC cells-of-origin and their prognosis
2022-08-29 | E-MTAB-11856 | biostudies-arrayexpress
Project description:Keratinocyte cancers (KC) are the most prevalent malignancies in fair-skinned populations, posing a significant medical and economic burden to health systems. KC originate in the epidermis and mainly comprise basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Here we combined single-cell multi-omics, transcriptomics and methylomics to investigate the epigenomic dynamics during epidermal differentiation. We identified ~4,000 differentially accessible regions between undifferentiated and differentiated keratinocytes, corresponding to regulatory regions associated with key transcription factors. DNA methylation at these regions defined AK/cSCC subtypes with epidermal stem cell- or keratinocyte-like features. Using cell type deconvolution tools and integration of bulk and single-cell methylomes, we demonstrate that these subclasses are consistent with distinct cells-of-origin. Further characterization of the phenotypic traits of the subclasses, and the study of additional unstratified KC entities uncovered distinct clinical features for the subclasses, linking invasive and metastatic KC cases with undifferentiated cells-of-origin. Our study provides a thorough characterization of the epigenomic dynamics underlying human keratinocyte differentiation and uncovers novel links between KC cells-of-origin and their prognosis.
2022-11-28 | GSE208304 | GEO
Project description:Keratinocyte cancers (KC) are the most prevalent malignancies in fair-skinned populations, posing a significant medical and economic burden to health systems. KC originate in the epidermis and mainly comprise basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Here, we combined single-cell transcriptomics, methylomics and multi-omics to investigate the epigenomic dynamics during epidermal differentiation. We identified ~4,000 differentially accessible regions between undifferentiated and differentiated keratinocytes, corresponding to regulatory regions associated with key transcription factors. DNA methylation at these regions defined AK/cSCC subtypes with epidermal stem cell- or keratinocyte-like features. Using cell type deconvolution tools and integration of bulk and single-cell methylomes, we demonstrate that these subclasses are consistent with distinct cells-of-origin. Further characterization of the subclasses with an epigenetic mitotic-like clock, and the study of other unstratified KC entities uncovered distinct phenotypic and clinical features for the subclasses, linking invasive and metastatic KC cases with undifferentiated cells-of-origin. Our study provides a thorough characterization of the epigenomic dynamics underlying human keratinocyte differentiation and uncovers novel links between KC cells-of-origin and their prognosis
2022-08-30 | GSE207335 | GEO
Project description:Keratinocyte cancers (KC) are the most prevalent malignancies in fair-skinned populations, posing a significant medical and economic burden to health systems. KC originate in the epidermis and mainly comprise basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Here, we combined single-cell transcriptomics, methylomics and multi-omics to investigate the epigenomic dynamics during epidermal differentiation. We identified ~4,000 differentially accessible regions between undifferentiated and differentiated keratinocytes, corresponding to regulatory regions associated with key transcription factors. DNA methylation at these regions defined AK/cSCC subtypes with epidermal stem cell- or keratinocyte-like features. Using cell type deconvolution tools and integration of bulk and single-cell methylomes, we demonstrate that these subclasses are consistent with distinct cells-of-origin. Further characterization of the subclasses with an epigenetic mitotic-like clock, and the study of other unstratified KC entities uncovered distinct phenotypic and clinical features for the subclasses, linking invasive and metastatic KC cases with undifferentiated cells-of-origin. Our study provides a thorough characterization of the epigenomic dynamics underlying human keratinocyte differentiation and uncovers novel links between KC cells-of-origin and their prognosis
2022-08-30 | GSE207336 | GEO