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Tension sensing by FAK governs nuclear mechanotransduction, trancriptome and fate endothelial transcriptome and fate

ABSTRACT: Tension sensing by FAK governs nuclear mechanotransduction, trancriptome and fate endothelial transcriptome and fate

PROVIDER: PRJNA873685 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21200806.fastq.gz	Fastqsanger.gz
	SRR21200807.fastq.gz	Fastqsanger.gz
	SRR21200808.fastq.gz	Fastqsanger.gz
	SRR21200809.fastq.gz	Fastqsanger.gz
	SRR21200810.fastq.gz	Fastqsanger.gz

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Similar Datasets

Tension sensing by FAK governs nuclear mechanotransduction, trancriptome and fate endothelial transcriptome and fate

Project description:Endothelial cell (EC) attachment to the matrix and adjacent cells generates a mechanical environment that maintains a restrictive barrier against the uncontrolled influx of circulating protein and immune cells. Mechanisms that mediate the transition from restrictive to leaky endothelium, a hallmark of tissue injury exemplified by acute lung injury (ALI), remain elusive. Here, we show that FAK sensing and transmission of mechanical tension to the EC nucleus governs cell fate. In FAK-deleted EC, increased EC tension activated DNMT3a, which induced methylation of the KLF2 promoter leading to impaired synthesis of KLF2 and restrictive EC transcriptome, including S1PR1. FAK suppressed DNMT3a activity by restricting the tyrosine phosphorylation of nuclear envelope protein, emerin at Y74/Y95, and its localization in a nuclear cap. Inhibiting emerin phosphorylation or DNMT3a activity in damaged lungs enabled KLF2 transcription of S1PR1, rescuing the restrictive EC phenotype. Our works reveal a paradigm whereby FAK sensing of tension transmission to the nucleus maintains restrictive EC transcriptome and lung homeostasis.

2022-08-28 | GSE212037 | GEO

FAK is required for suppressing aberrant nuclear mechanotransduction and DNA methylation to prevent vascular injury

Project description:Mechanical forces generated through adhesive interaction of endothelial cells (EC) influence nuclear envelope and thereby gene transcription. Alteration in EC mechanical forces may trigger aberrant gene transcription leading to lethal vascular diseases including acute lung injury (ALI). The intrinsic pathways that instruct EC nuclear-mechanotransduction and thereby maintains vascular homeostasis remain elusive. We have identified focal adhesion kinase (FAK)-mediated mechanotransduction at the nuclear envelope in instructing transcription of EC-barrier protective genes. We show that loss of EC-FAK increases intracellular tension, which in turn activates nuclear envelop protein emerin, and DNA methyltransferase 3a (DNMT3a). Methylation of transcription factor KLF2 promoter by DNMT3a impaired KLF2 synthesis and transcription of the crucial barrier-maintaining gene, S1PR1. Restoring KLF2 or S1PR1 expression or impairing emerin or DNMT3a activity rescued vascular homeostasis in lungs with FAK-deficient or WT-damaged endothelium. Thus, FAK protects against tension-induced aberrant DNA methylation in EC and is a promising target to prevent ALI.

2022-07-11 | GSE207789 | GEO

Membrane tension regulated mechanotransduction drives fate transitions in embryonic stem cells

Project description:Membrane tension regulated mechanotransduction drives fate transitions in embryonic stem cells

| PRJNA668927 | ENA

Membrane tension regulated mechanotransduction drives fate transitions in embryonic stem cells

Project description:Changes in cell shape and mechanics frequently accompany cell fate transitions. Yet how cellular mechanics affects the regulatory pathways controlling cell fate is poorly understood. To probe the interplay between shape, mechanics and fate, we used embryonic stem (ES) cells, which spread as they undergo early differentiation. We found that this spreading is regulated by a β-catenin mediated decrease in RhoA activity and subsequent decrease in the plasma membrane tension. Strikingly, preventing the membrane tension decrease resulted in early differentiation defects in ES cells and gastruloids. We further find that the decrease in membrane tension facilitates endocytosis of FGF signaling components, which activates ERK signaling and directs exit from the ES cell state. The early differentiation defects we observed can be rescued by increasing Rab5afacilitated endocytosis. Thus, we show that a mechanically-triggered increase in endocytosis regulates early differentiation. Our findings are of fundamental importance for understanding how cell mechanics regulates biochemical signaling, and therefore cell fate.

2020-10-14 | GSE159433 | GEO

Defining the role of oxygen tension in human neural progenitor fate

Project description:Hypoxia augments human embryonic stem cell self-renewal via hypoxia-inducible factor 2M-NM-1 (HIF2M-NM-1) activated OCT4 (POU5F1) transcription. Hypoxia also increases the efficiency of reprogramming differentiated cells to a pluripotent-like state. Combined, these findings suggest that low oxygen (O2) tension would impair the purposeful differentiation of pluripotent stem cells. Here, we show that low O2 tension and HIF activity instead promotes appropriate hESC differentiation. Through gain and loss of function studies, we implicate O2 tension as a modifier of a key cell fate decision, namely whether neural progenitors differentiate towards neurons or glia. Furthermore, our data show that even transient changes in O2 concentration can affect cell fate through HIF by regulating the activity of MYC, a regulator of LIN28/let-7 that is critical for fate decisions in the neural lineage. We also identify key small molecules that can take advantage of this pathway to quickly and efficiently promote the development of mature cell types. We used microarrays to detail the global gene expression of human neural progenitor cells (NPC) cultured in physiological (2%) oxygen tension. By comparing NPCs with activated Hypoxia inducible factor (HIF) activity (DFX treatment) and NPCs with diminished HIF activity (HIF1M-NM-2 knockdown), we identified genes that are important for NPC fate decision under physiological oxygen concentration. We also used microarrays to obtain a global gene expression profiling during embryoid bodies formation using ES cells with diminished HIF activity. In HIF activation experiments, two ES lines and one iPS line-derived NPC were used, with or without DFX treatment for 5 days. In HIF1M-NM-2 knockdown experiments, NPCs were derived from either shHIF1M-NM-2 or control ES lines. In embryoid body formation experiments, day0 (ES stage) and day6 EBs were generated from either shHIF1M-NM-2 or control ES lines in 2% oxygen.

2014-09-30 | E-GEOD-61842 | biostudies-arrayexpress

Defining the role of oxygen tension in human neural progenitor fate

Project description:Hypoxia augments human embryonic stem cell self-renewal via hypoxia-inducible factor 2α (HIF2α) activated OCT4 (POU5F1) transcription. Hypoxia also increases the efficiency of reprogramming differentiated cells to a pluripotent-like state. Combined, these findings suggest that low oxygen (O2) tension would impair the purposeful differentiation of pluripotent stem cells. Here, we show that low O2 tension and HIF activity instead promotes appropriate hESC differentiation. Through gain and loss of function studies, we implicate O2 tension as a modifier of a key cell fate decision, namely whether neural progenitors differentiate towards neurons or glia. Furthermore, our data show that even transient changes in O2 concentration can affect cell fate through HIF by regulating the activity of MYC, a regulator of LIN28/let-7 that is critical for fate decisions in the neural lineage. We also identify key small molecules that can take advantage of this pathway to quickly and efficiently promote the development of mature cell types. We used microarrays to detail the global gene expression of human neural progenitor cells (NPC) cultured in physiological (2%) oxygen tension. By comparing NPCs with activated Hypoxia inducible factor (HIF) activity (DFX treatment) and NPCs with diminished HIF activity (HIF1β knockdown), we identified genes that are important for NPC fate decision under physiological oxygen concentration. We also used microarrays to obtain a global gene expression profiling during embryoid bodies formation using ES cells with diminished HIF activity.

2014-09-30 | GSE61842 | GEO

CCM3 is a gatekeeper in focal adhesions regulating mechanotransduction and YAP/TAZ signalling

Project description:We report that loss of CCM3/PDCD10 in fibroblasts induces FAK/Src-paxillin signalling driving actomyosin-dependent mechanotransduction leading to YAP/TAZ signalling. In vivo, loss of CCM3 in fibroblasts drives excessive tissue remodelling leading to the dissemination of breast cancer cells to distant organs.

2021-05-06 | GSE155688 | GEO

FAK is required for suppressing aberrant nuclear mechanotransduction and DNA methylation to prevent vascular injury

Project description:FAK is required for suppressing aberrant nuclear mechanotransduction and DNA methylation to prevent vascular injury

| PRJNA857070 | ENA

Mechanotransduction mediated by cyclical respiratory motion maintains lung alveolar epithelial cell fate

Project description:Mechanotransduction mediated by cyclical respiratory motion maintains lung alveolar epithelial cell fate

| PRJNA835452 | ENA

Role of FAK, dominant-negative FAK, FAK-CD and FAKsiRNA in MCF-7 human breast cancer cell tumorigenesis

Project description:Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays an important role in proliferation, motility, adhesion, invasion, angiogenesis, and survival signaling. Focal adhesion kinase has been shown to be overexpressed in many types of tumors, including breast cancer at early stages of tumorigenesis. To study the biological role of FAK in breast tumorigenesis, we used FAKsiRNA to down-regulate FAK in MCF-7 cell lines.

2009-08-17 | GSE11581 | GEO

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