Time-resolved function of cell polarity kinases PRKCZ and PRKCI in CNS myelination [snrna_oligo]
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ABSTRACT:
PROVIDER: PRJNA1100500 | ENA |
REPOSITORIES: ENA
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Project description:The atypical Protein Kinase C (aPKC) is a critical component of the PAR polarity complex, as well as of cell polarity in general. There are two paralogs of aPKC in the mammalian genome. Their expression pattern and functional role in oligodendrocyte lineage differentiation and development remains heretofore uncharacterized. Here we show that both paralogs of aPKC – PRKCI, the primary transcript of Prkci and PKMz, an alternate transcript of Prkcz – are expressed during oligodendrocyte differentiation, yet are functionally non-redundant. Asymmetric cell division and early specification of the oligodendrocyte fate stage required both paralogs. By contrast, the stage of oligodendrocyte maturation involving membrane polarization and myelination of axons continued to require PKMz, but no longer needed PRKCI. Taken together, our results indicate to a two-stage role of aPKCs and cell polarity in oligodendrocyte differentiation and development.
2024-04-21 | GSE263981 | GEO
Project description:The atypical Protein Kinase C (aPKC) is a critical component of the PAR polarity complex, as well as of cell polarity in general. There are two paralogs of aPKC in the mammalian genome. Their expression pattern and functional role in oligodendrocyte lineage differentiation and development remains heretofore uncharacterized. Here we show that both paralogs of aPKC – PRKCI, the primary transcript of Prkci and PKMz, an alternate transcript of Prkcz – are expressed during oligodendrocyte differentiation, yet are functionally non-redundant. Asymmetric cell division and early specification of the oligodendrocyte fate stage required both paralogs. By contrast, the stage of oligodendrocyte maturation involving membrane polarization and myelination of axons continued to require PKMz, but no longer needed PRKCI. Taken together, our results indicate to a two-stage role of aPKCs and cell polarity in oligodendrocyte differentiation and development.
2024-04-21 | GSE263979 | GEO
Project description:Time-resolved function of cell polarity kinases PRKCZ and PRKCI in CNS myelination [bulk_oligo]
| PRJNA1100495 | ENA
Project description:A key feature of serous ovarian cancer is frequent amplification in the 3q26 locus, which harbors the PRKCI gene. Here we show that PRKCI is amplified and overexpressed in a 78% of high-grade serous ovarian carcinoma. Our in vivo studies with orthotopic mouse models establish it as an ovarian cancer oncogene. This oncogenic property of PRKCI is mediated by regulation of YAP1 activity. Accordingly YAP1 knockdown partially rescues PRKCI mediated tumorigenesis. Integrated gene expression profiling and YAP1 promoter occupancy analyses reveal that PRKCI and YAP1 cooperate to transcriptionally regulate genes affecting the tumor immune microenvironment. Consistently, CD11b+Gr1+Ly6G+ MDSCs are increased in the tumor microenvironment of PRKCI over-expressing tumors. Importantly, we show that elevated PRKCI expression in high-grade serous ovarian carcinomas strongly correlated with assignment to immunoreactive subtype. In summary, we identify PRKCI and YAP1 as key mediators of a tumor-promoting immunosuppressive microenvironment in ovarian cancers.
2018-01-15 | GSE57257 | GEO
Project description:A key feature of serous ovarian cancer is frequent amplification in the 3q26 locus, which harbors the PRKCI gene. Here we show that PRKCI is amplified and overexpressed in a 78% of high-grade serous ovarian carcinoma. Our in vivo studies with orthotopic mouse models establish it as an ovarian cancer oncogene. This oncogenic property of PRKCI is mediated by regulation of YAP1 activity. Accordingly YAP1 knockdown partially rescues PRKCI mediated tumorigenesis. Integrated gene expression profiling and YAP1 promoter occupancy analyses reveal that PRKCI and YAP1 cooperate to transcriptionally regulate genes affecting the tumor immune microenvironment. Consistently, CD11b+Gr1+Ly6G+ MDSCs are increased in the tumor microenvironment of PRKCI over-expressing tumors. Importantly, we show that elevated PRKCI expression in high-grade serous ovarian carcinomas strongly correlated with assignment to immunoreactive subtype. In summary, we identify PRKCI and YAP1 as key mediators of a tumor-promoting immunosuppressive microenvironment in ovarian cancers.
2018-01-15 | GSE57236 | GEO
Project description:RNA-seq analysis was performed on TICs and the parental counterparts of 4 LSCC cell lines. In addition, PRKCI knock down (KD) variants of these cells were sequenced. Subsequent analysis revealed that activation of HH signaling, a known driver of the TIC phenotype, is dependent on PRKCI expression. Examination of TICS, parental cells, parental PRKCI KD cells, and TIC PRKCI KD cells
2014-03-28 | E-GEOD-48599 | biostudies-arrayexpress
Project description:A key feature of ovarian high-grade serous carcinoma is frequent amplification of the 3q26 locus. Here we show that PRKCI, located on the 3q26 locus is not only amplified and overexpressed in 78% of HGSC patient samples but is also expressed in early fallopian tube lesions, called Serous Tubal Intraepithelial Carcinoma. In vivo studies in a transgenic mouse model establish PRKCI as an ovarian cancer oncogene and identify YAP1 as a downstream regulator. Together, PRKCI and YAP1 regulate TNFα to promote an immune suppressive microenvironment and inhibit cytotoxic T-cell infiltration in tumors. High PRKCI expressing human ovarian tumors show decreased cytotoxic T-cell infiltration. Taken together, we identify PRKCI and YAP1 as key mediators of a tumor-promoting immune microenvironment in ovarian cancer.
2018-06-01 | GSE57262 | GEO
Project description:A key feature of high-grade serous ovarian carcinoma (HGSOC) is frequent amplification of the 3q26 locus harboring PRKC-iota (PRKCI). Here, we show that PRKCI is also expressed in early fallopian tube lesions, called Serous Tubal Intraepithelial Carcinoma. Transgenic mouse studies establish PRKCI as an ovarian cancer specific oncogene and system level and functional analyses identify YAP1 as a downstream effector in tumor progression. Mechanistically, the oncogenic activity of the PRKCI-YAP1 axis relates in part to the upregulation of TNFα to promote an immune suppressive tumor microenvironment characterized by an abundance of myeloid-derived suppressor cells and inhibition of cytotoxic T cell infiltration. In human ovarian cancers, high PRKCI expression also correlates with high expression of YAP1 and low infiltration of cytotoxic T-cell. The PRKCI-YAP1 regulation of the tumor immunity provides a therapeutic strategy for highly lethal ovarian cancer. Robust multi-array average (RMA) method was used with default options (with background correction, quantile normalization, and log transformation) to normalize raw data from batches using R/Bioconductor‘s affy package
2018-06-01 | GSE82319 | GEO
Project description:In order to investigate the crucial role of PRKCI in glioblastoma stem-like cell (GSC) survival, gene expression microarray-based transcriptome analysis was conducted on GSCs transduced for 4 days with PRKCI shRNA compared with GSCs transduced with shNT.
2016-01-21 | GSE77030 | GEO
Project description:Myelination of neuronal axons is essential for nervous system development. Myelination requires dramatic cytoskeletal dynamics in oligodendrocytes, but how actin is regulated during myelination is poorly understood. We recently identified serum response factor (SRF)—a transcription factor known to regulate expression of actin and actin regulators in other cell types—as a critical driver of myelination in the aged brain. Yet, a major gap remains in understanding the fundamental role of SRF in oligodendrocyte lineage cells. Here we show that SRF is required cell autonomously in oligodendrocytes for myelination during development. Combining ChIP-seq with RNA-seq identifies SRF-target genes in OPCs and oligodendrocytes that include actin and other key cytoskeletal genes. Accordingly, SRF knockout oligodendrocytes exhibit dramatically reduced actin filament levels early in differentiation, consistent with its role in actin-dependent myelin sheath initiation. Together, our findings identify SRF as a transcriptional regulator that controls the expression of cytoskeletal genes required in oligodendrocytes for myelination. This study identifies a novel pathway regulating oligodendrocyte biology with high relevance to brain development, aging, and disease.
2024-02-23 | GSE241560 | GEO