Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The tetraspanin CD53 protects stressed hematopoietic stem cells via promotion of DREAM complex-mediated quiescence

ABSTRACT: The tetraspanin CD53 protects stressed hematopoietic stem cells via promotion of DREAM complex-mediated quiescence

PROVIDER: PRJNA906926 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR22461117.fastq.gz	Fastqsanger.gz
	SRR22461118.fastq.gz	Fastqsanger.gz
	SRR22461119.fastq.gz	Fastqsanger.gz
	SRR22461120.fastq.gz	Fastqsanger.gz
	SRR22461121.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 22

Similar Datasets

The tetraspanin CD53 protects stressed hematopoietic stem cells via promotion of DREAM complex-mediated quiescence

Project description:Hematopoietic stem cells (HSCs) cycle in response to inflammatory and other proliferative stressors; however, they must quickly return to quiescence to avoid exhaustion and maintain their functional integrity. The mechanisms that regulate this return to quiescence are not well understood. Here we show that the tetraspanin CD53 is markedly upregulated in HSCs in response to a variety of inflammatory and proliferative stimuli, and loss of CD53 is associated with prolonged cycling and reduced HSC function in the context of inflammatory stress. Mechanistically, CD53 promotes the activity of the DREAM transcriptional repressor complex, which downregulates genes associated with cycling and division. Proximity labeling and confocal fluorescent microscopy studies show that CD53 interacts with DREAM-associated proteins, specifically promoting the interaction between Rbl2/p130 and its phosphatase, PP2A, effectively stabilizing p130 protein availability for DREAM binding. Together, these data identify a novel mechanism by which stressed HSCs resist continued cycling.

2022-12-22 | GSE219050 | GEO

The tetraspanin CD53 protects stressed hematopoietic stem cells via promotion of DREAM complex-mediated quiescence.

Project description:The hematopoietic stem cell (HSC) cycle responds to inflammatory and other proliferative stressors; however, these cells must quickly return to quiescence to avoid exhaustion and maintain their functional integrity. The mechanisms that regulate this return to quiescence are not well understood. Here, we show that tetraspanin CD53 is markedly upregulated in HSCs in response to a variety of inflammatory and proliferative stimuli and that the loss of CD53 is associated with prolonged cycling and reduced HSC function in the context of inflammatory stress. Mechanistically, CD53 promotes the activity of the dimerization partner, RB-like, E2F, and multi-vulva class B (DREAM) transcriptional repressor complex, which downregulates genes associated with cycling and division. Proximity labeling and confocal fluorescence microscopy studies showed that CD53 interacts with DREAM-associated proteins, specifically promoting the interaction between Rbl2/p130 and its phosphatase protein phosphatase 2A (PP2A), effectively stabilizing p130 protein availability for DREAM binding. Together, these data identified a novel mechanism by which stressed HSCs resist cycling.

| S-EPMC10023726 | biostudies-literature

Lin37 is essential for repression of cell-cycle genes in quiescence

Project description:The DREAM complex represses cell-cycle gene transcription in quiescence. To investigate the role of the DREAM component Lin37, we created Lin37 knockout cells by CRISPR/Cas9-nickase. pRTS episomal vectors expressing luciferase or Lin37 were introduced in two independent knockout clones (411-27 and 632-2) to create Lin37 knockout and rescue cells. To exit the cell cycle and to enter quiescence, cells were serum starved for 60h. RNA-seq was applied to identify genes de-regulated by loss of Lin37 during quiescence.

2017-08-17 | GSE97716 | GEO

DREAM represses distinct targets by cooperating with different THAP domain proteins [RNA-seq]

Project description:The DREAM (DP, Retinoblastoma [Rb]-like, E2F, and MuvB) complex controls cellular quiescence by repressing cell cycle and other genes, but its mechanism of action is unclear. Here we demonstrate that two C. elegans THAP domain proteins, LIN-15B and LIN-36, co-localize with DREAM and function by different mechanisms for repression of distinct sets of targets. LIN-36 represses classical cell cycle targets by promoting DREAM binding and gene body enrichment of H2A.Z. Furthermore, the function of DREAM subunit EFL-1/E2F is specific for LIN-36 targets. In contrast, LIN-15B represses a subset of germline targets by facilitating H3K9me2 promoter marking. In humans, THAP proteins have been implicated in cell cycle regulation by poorly understood mechanisms. We propose that THAP domain proteins are key mediators of Rb/DREAM function, facilitating repression of distinct sets of targets.

2020-08-13 | GSE155190 | GEO

DREAM represses distinct targets by cooperating with different THAP domain proteins [CHIP-seq]

2020-08-13 | GSE155189 | GEO

DREAM, a Possible Answer to the Estrogen Paradox of the Women’s Health Initiative Trial

Project description:Estrogen is thought to cause proliferation of all estrogen receptor positive (ER+) breast cancers. Paradoxically, in the Women’s Health Initiative Trial, estrogen-only hormone replacement therapy reduced the incidence and mortality of low grade, ER+, HER2- breast cancer. We gave estradiol to 19 post-menopausal women with newly diagnosed low-grade, ER+, HER2- breast cancer in a prospective window of opportunity clinical trial and examined the changes in proliferation and gene expression before and after estradiol treatment. Ki67 decreased in 13/19 (68%) patients and 8/13 (62%) showed a decrease in Risk of Recurrence Score. We chose three prototypical estrogen responders (greatest decrease in ROR) and non-responders (no/minimal change in ROR) and applied a differential gene expression analysis to develop pre-treatment (PRESTO-30core) and post-treatment (PRESTO-45surg) gene expression profiles. The PRESTO-30core predicted adjuvant benefit in a published series of tamoxifen, the partial estrogen agonist. Of the 45 genes in the PRESTO-45surg, thirty contain the Cell cycle genes Homology Region (CHR) motif that binds the class B multi-vulva complex (MuvB) a member of the DREAM (Dimerization partner, retinoblastoma-like proteins, E2F, MuvB) complex responsible for reversible cell cycle arrest or quiescence. There was also near uniform suppression (89%) of the remaining DREAM genes consistent with estrogen induced activation of the DREAM complex to mediate cell cycle block after a short course of estrogens. To our knowledge, this is the first report to show hormonal modulation of DREAM genes and suggest involvement of DREAM pathway associated quiescence in endocrine responsive post-menopausal ER+ breast cancers.

2021-12-27 | GSE139688 | GEO

The DREAM complex functions as conserved master regulator of somatic DNA repair capacities

Project description:Mutations in the DREAM complex induce germline-like gene expression patterns including the increase of multiple mechanisms of DNA repair in the soma of Caenorhabditis elegans. This confers mutants of the DREAM complex resistance to a wide range of DNA damage types during development and aging.

2023-01-31 | PXD033836 | Pride

DREAM On, DREAM Off: A Review of the Estrogen Paradox

Project description:DREAM On, DREAM Off: A Review of the Estrogen Paradox

| PRJNA1114009 | ENA

DREAM in pain mechanisms in the trigeminal ganglia

Project description:Expression of DREAM in dorsal root ganglia and spinal cord is related to endogenous control mechanisms of acute and chronic pain. In primary sensory trigeminal neurons high levels of endogenous DREAM protein are preferentially localized in the nucleus, suggesting a major transcriptional role. Here, we show that DREAM participates in the control of trigeminal pain perception through the regulation of prodynorphin and BDNF. Furthermore, genome-wide analysis of trigeminal neurons in daDREAM transgenic mice revealed that cathepsin L (CTSL) and the monoglyceride lipase (MGLL) are new DREAM downstream targets and have a role in the regulation of trigeminal nociception.

2016-04-22 | GSE69619 | GEO

Drosophila Myb-MuvB/dREAM

Project description:Drosophila Myb-MuvB/dREAM

| PRJNA102609 | ENA