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| Status |
Public on Nov 20, 2018 |
| Title |
TFEB controls vascular development by regulating the proliferation of endothelial cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The role of the transcription factor EB (TFEB) in the control of cellular functions, including in vascular bed, is mostly thought to be the regulation of lysosomal biogenesis and autophagic flux. While this is its best-known function, we report here the ability of TFEB to orchestrate a non-canonical program involved in the control of cell-cycle and VEGFR2 pathway in the developing vasculature. In endothelial cells, TFEB deletion halts proliferation by inhibiting the CDK4/Rb pathway, which regulates the cell cycle G1-S transition. In an attempt to overcome this limit, cells compensate by increasing the amount of VEGFR2 on the plasma membrane through a microRNA-mediated mechanism and the control of its membrane trafficking. TFEB transactivates the miR-15a/16-1 cluster, which limits the stability of the VEGFR2 transcript, and negatively modulates the expression of MYO1C, which regulates VEGFR2 delivery to the cell surface. In TFEB knocked-down cells, the reduced and increased amount respectively of miR-15a/16-1 and MYO1C result in the overexpression on plasmamembrane of VEGFR2, which however shows low signaling strength. Using endothelial loss-of-function Tfeb mouse mutants, we present evidence of defects in fetal and newborn mouse vasculature caused by the reduced endothelial proliferation and by the anomalous function of VEGFR2 pathway. Thus, this study revealed a new and unreported function of TFEB that expands its role beyond the regulation of autophagic pathway in the vascular system.
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| Overall design |
This SuperSerie is composed of the SubSeries listed below. In the first experiment we report the ChIP-seq of the TFEB transcription factor in a model of HUVEC cells. In the second one, we study the effect of the down-modulation of the TFEB transcription factor, in the same model.
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| |
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| Citation(s) |
30591554 |
| Submission date |
Oct 18, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Davide Cora' |
| E-mail(s) |
davide.cora@ircc.it, davide.cora@uniupo.it
|
| Phone |
+390321660631
|
| Organization name |
Piemonte Orientale University and IRCCS Candiolo Cancer Institute
|
| Department |
Dept. of Oncology
|
| Lab |
Vascular Oncology
|
| Street address |
Str. Prov. 142 Km. 3.95
|
| City |
Candiolo |
| State/province |
TO |
| ZIP/Postal code |
I-10060 |
| Country |
Italy |
| |
|
| Platforms (2) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (8)
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| This SuperSeries is composed of the following SubSeries: |
| GSE88894 |
TFEB controls vascular development by regulating the proliferation of endothelial cells (TFEB ChIp-seq) |
| GSE88895 |
TFEB controls vascular development by regulating the proliferation of endothelial cells (sh-TFEB marray) |
|
| Relations |
| BioProject |
PRJNA349032 |
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