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A MYC-driven change in mitochondrial dynamics limits stem cell properties of mammary epithelial cells

ABSTRACT: A MYC-driven change in mitochondrial dynamics limits stem cell properties of mammary epithelial cells

PROVIDER: PRJNA276280 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1817570.fastq.gz	Fastqsanger.gz
	SRR1817580.fastq.gz	Fastqsanger.gz
	SRR1817571.fastq.gz	Fastqsanger.gz
	SRR1817581.fastq.gz	Fastqsanger.gz
	SRR1817572.fastq.gz	Fastqsanger.gz

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A MYC-driven change in mitochondrial dynamics limits stem cell properties of mammary epithelial cells (ChIP-seq)

Project description:In several developmental lineages, an increase in expression of the MYC proto-oncogene drives the transition from quiescent stem cells to transit amplifying cells. The mechanism by which MYC restricts self-renewal of adult stem cells is unknown. Here, we show that MYC activates a stereotypic transcriptional program of genes involved in protein translation and mitochondrial biogenesis in mammary epithelial cells and indirectly inhibits the YAP/TAZ co-activators that are essential for mammary stem cell self-renewal. We identify a phospholipase of the mitochondrial outer membrane, PLD6, as the mediator of MYC activity. PLD6 mediates a change in the mitochondrial fusion/fission balance that promotes nuclear export of YAP/TAZ in a LATS- and RHO-independent manner. Mouse models and human pathological data confirm that MYC suppresses YAP/TAZ activity in mammary tumors. PLD6 is also required for glutaminolysis, arguing that MYC-dependent changes in mitochondrial dynamics balance cellular energy metabolism with the self-renewal potential of adult stem cells. ChIP-Seq experiments for MYC-HA (HA-IP) performed in IMEC primary breast epithelial cells. Input-samples were sequenced as controlls.

2015-10-28 | E-GEOD-66252 | biostudies-arrayexpress

A MYC-driven change in mitochondrial dynamics limits stem cell properties of mammary epithelial cells (RNA-seq)

Project description:In several developmental lineages, an increase in expression of the MYC proto-oncogene drives the transition from quiescent stem cells to transit amplifying cells. The mechanism by which MYC restricts self-renewal of adult stem cells is unknown. Here, we show that MYC activates a stereotypic transcriptional program of genes involved in protein translation and mitochondrial biogenesis in mammary epithelial cells and indirectly inhibits the YAP/TAZ co-activators that are essential for mammary stem cell self-renewal. We identify a phospholipase of the mitochondrial outer membrane, PLD6, as the mediator of MYC activity. PLD6 mediates a change in the mitochondrial fusion/fission balance that promotes nuclear export of YAP/TAZ in a LATS- and RHO-independent manner. Mouse models and human pathological data confirm that MYC suppresses YAP/TAZ activity in mammary tumors. PLD6 is also required for glutaminolysis, arguing that MYC-dependent changes in mitochondrial dynamics balance cellular energy metabolism with the self-renewal potential of adult stem cells. RNA-Seq Experiments in 2 different primary breast epithelial cell lines (HMLE, which were sorted according to CD44/CD24 surface markers & unsorted IMEC). Both cell lines expressed a doxycycline-inducible version of MYC. For the HMLE cell line DGE analysis was performed for the uninduced (EtOH) situation, comparing CD44high vs CD44 low and for the induced situation Dox vs. EtOH for the CD44high population. For the IMEC cell line DGE was performed by comparing Dox-treated populations expressing either Dox-inducible MYC or a vector control which allows to filter out potential effects due to doxycycline treatment.

2015-10-28 | E-GEOD-66250 | biostudies-arrayexpress

A MYC-driven change in mitochondrial dynamics limits stem cell properties of mammary epithelial cells (ChIP-seq)

2015-10-28 | GSE66252 | GEO

A MYC-driven change in mitochondrial dynamics limits stem cell properties of mammary epithelial cells (RNA-seq)

2015-10-28 | GSE66250 | GEO

A MYC-driven change in mitochondrial dynamics limits stem cell properties of mammary epithelial cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-10-28 | E-GEOD-66263 | biostudies-arrayexpress

A MYC-driven change in mitochondrial dynamics limits stem cell properties of mammary epithelial cells

Project description:This SuperSeries is composed of the SubSeries listed below.

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Stem cell-like properties of CK2β-downregulated mammary cells

Project description:Stem cell-like properties of CK2β-downregulated mammary cells

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Stem cell-like properties of CK2β-downregulated mammary cells [mRNA]

Project description:The ubiquitous Protein kinase CK2 has been demonstrated to be overexpressed in a number of human tumors. This enzyme is composed of two catalytic α or α’ subunits and a dimer of β regulatory subunits whose expression levels are probably implicated in CK2 regulation. Several recent papers reported that unbalanced expression of CK2 subunits is sufficient to drive epithelial to mesenchymal transition, a process involved in cancer invasion and metastasis. Herein, through transcriptomic and miRNA analysis together with comparison of cellular properties between wild type and CK2β-knock-down MCF10A cells, we show that down-regulation of CK2β subunit in mammary epithelial cells induces the acquisition of stem cell-like properties associated with CD44high/CD24low antigenic phenotype and the ability to grow under anchorage-independent conditions. These data demonstrate that a CK2β level establishes a critical cell fate threshold in the control of epithelial cell plasticity. Thus, this regulatory subunit functions as a nodal protein to maintain an epithelial phenotype.

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Project description:A MYC-driven change in mitochondrial dynamics limits stem cell properties of mammary epithelial cells (RNA-seq)

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