TAp73 functions through posttranscriptional codes in brain multiciliogenesis
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE108385 | GEO | 2019/05/21
REPOSITORIES: GEO
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Project description:TAp73 functions through posttranscriptional codes in brain multiciliogenesis
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Project description:TAp73 is a master regulator of airway multiciliogenesis
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Project description:Comparative RNA seq analysis of WT and global p73KO Mouse Tracheal Epithelial Cell (MTECs) during the course of their differentiation (Air-Liquid Interface ALI D0, D4, D7, D14) aimed to determine the role of p73 in motile multiciliogenesis.
2016-05-05 | GSE75715 | GEO
Project description:Comparative small RNA seq analysis of WT and global p73KO Mouse Tracheal Epithelial Cell (MTECs) during the course of their differentiation (Air-Liquid Interface ALI D0, D4, D7, D14) aimed to determine the role of p73 in motile multiciliogenesis.
2016-05-05 | GSE75716 | GEO
Project description:The aim of the experiment was to analyse the gene expression differences between MEFs containing TAp73 or without TAp73, at basal levels in normal culture conditions, and upon treatment with hypoxia (by incubation in 1% oxygen) for 4 or 8 hrs. The analysis indicate that absence of TAp73 leads to changes in multiple cellular and biological processes.
2014-10-11 | GSE62236 | GEO
Project description:The aim of the experiment was to analyse the gene expression differences between MEFs containing TAp73 or without TAp73, at basal levels in normal culture conditions, and upon treatment with hypoxia (by incubation in 1% oxygen) for 4 or 8 hrs. The analysis indicate that absence of TAp73 leads to changes in multiple cellular and biological processes. TAp73-/- and Tap73+/+ MEFs that were untreated, or treated with hypoxia (in 1% oxygen) for 4 and 8 hours were used for gene expression analysis
2014-10-11 | E-GEOD-62236 | biostudies-arrayexpress
Project description:Multiciliated cells are crucial for fluid and ion transport in epithelia of a variety of organs and their impaired development and function are seen in human diseases affecting the brain, respiratory, and reproductive tracts. Multiciliogenesis requires activation of a specialized transcription program coupled to complex cytoplasmic events that lead to large-scale centriole amplification to generate multicilia. Yet, it remains unclear how these events are coordinated to initiate multiciliogenesis in epithelial progenitors. Here we identify an unsuspected mechanism orchestrated by the transcription factor E2f4 essential to integrate these processes. We show that after inducing a transcriptional program of centriole biogenesis, E2f4 translocates to the cytoplasm to become a core component of structures classically identified as fibrous granules (FG), acting as organizing centers for deuterosome assembly and centriole amplification. Remarkably, loss of cytoplasmic E2f4 prevents FG aggregation, deuterosome assembly and multicilia formation even when E2f4’s transcriptional function is preserved. Moreover, in E2f4-deficient cells multiciliogenesis is rescued only if both nuclear and cytoplasmic E2f4 activities are restored. Thus, E2f4 integrates previously unrelated nuclear and cytoplasmic events of the multiciliated cell program.
2017-08-30 | GSE73331 | GEO
Project description:Multiciliated cells possess multiple motile cilia on the cell surface and are widely distributed throughout the vertebrate body to perform important physiological functions by regulating fluid movement in the intercellular space. However the molecular mechanisms underlying multiciliogenesis are not well understood. Although dysregulation of members of the miR-34 family plays a critical role in the progression of various cancers, the physiological function of miR-34b, especially in regulating multiciliogenesis, is largely unknown. Here we focus on the multiciliated cells in the zebrafish kidney to study whether and how miR-34b regulate multiciliogenesis. We performed genome-wide gene expression profiling of zebrafish kidney multiciliated cells in the absence (miR-34b morpholino) or presence of miR-34b (control morpholino). RNA samples for microarray gene expression profiling were collected at 3 days post fertilization.
2013-06-14 | E-MEXP-3893 | biostudies-arrayexpress
Project description:Hepatocyte dedifferentiation is a major source of hepatocellular carcinoma (HCC), but its mechanisms are unknown. We explored the p73 expression in HCC tumors and studied the effects of transcriptionally active p73 (TAp73) in HCC cells. Expression profiles of p73 and patient clinical data were collected from the Genomic Data Commons (GDC) data portal and the TSVdb database, respectively. Global gene expression profiles were determined by pan-genomic 54K microarrays. The Gene Set Enrichment Analysis was used to identify TAp73-regulated gene sets. The effects of TAp73 were analyzed in monolayer cell culture, 3D-tumoroid and xenograft models in zebrafish using western blot, flow cytometry, fluorescence imaging, real-time polymerase chain reaction (RT-PCR), immunohistochemistry and morphological examination. TAp73 was significantly upregulated in HCC, and its high expression indicated poor patient survival. The induced expression of TAp73 caused landscape expression changes including genes involved in growth signaling, cell cycle, stress response, immunity, metabolism and development. HCC cells overexpressing TAp73 had lost hepatocyte lineage biomarkers including ALB, CYP3A4, AFP, HNF4α. In contrast, TAp73 upregulated genes promoting cholangiocyte lineage such as YAP, JAG1 and ZO-1, accompanied with an increase in metastatic ability. Our findings strongly suggest that TAp73 is a major promoter of malignant dedifferentiation of HCC cells Hepatocellular carcinoma (HCC) is a highly complex and heterogeneous type of cancer. Hepatocyte dedifferentiation is one of the important steps in the development of HCC. However, its molecular mechanisms are not well known. In this study, we report that TAp73 which is the major transcriptionally active form of p73 is overexpressed in HCC. Mechanically, TAp73 suppresses the expression of the hepatocyte markers including CYP3A4, AFP, ALB, HNF4a, while increasing the expression of several cholangiocyte markers in HCC cell lines. In conclusion, this report reveals a pro-oncogenic role for TAp73 in liver cancer.
2021-03-10 | GSE162860 | GEO
Project description:Cancer stem cells (CSCs) are resistant to conventional chemotherapy and are hence responsible for cancer relapse. Pluripotency is a characteristic of CSCs which allows them to rapidly proliferate while maintaining the ability to differentiate into various lineages. We found that TAp73, but not its homologue p53, is required for the pluripotency of CSCs. TAp73 knockdown (KD) decreased SOD1 levels, increased ROS production and disturbed metabolism which induced differentiation and abrogated pluripotency in CSCs. TAp73 related decrease in pluripotency is linked to increased autophagy and senescence in CSCs. Furthermore, TAp73 KD also decreased the levels of pluripotency factor Sox-2 within heterogeneous cancer cell lines. Interestingly, TAp73-deficient CSCs strongly lose tumorigenic potential in mice and tumors that did form had significantly lower levels of SOD1 and pluripotency marker Oct4. Our findings reveal a unique role of TAp73 in CSCs development that is important to consider while devising future therapeutic strategies against cancer.
2019-03-05 | PXD005407 | Pride