Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

EMP1 preserves hematopoietic stem cell potential under homeostasis and radiation-induced injury by alleviating ER stress

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE277445 | GEO | 2025/03/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

EMP1 preserves hematopoietic stem cell potential under homeostasis and radiation-induced injury by alleviating ER stress

Project description:To illustrate EMP1-interacting proteins, we performed co-immunoprecipitation (co-IP) followed by mass spectrometry using HSPCs (Lin-c-Kit+) to characterize protein interactomes of EMP1. Murine HSPCs (Lin-c-Kit+) were infected with retrovirus to force EMP1 overexpression (with HA tag). Then IgG or HA antibodies were used to conducted co-immunoprecipitation (co-IP), followed by and mass spectrometry analysis.

2025-03-13 | PXD055884 | Pride

EMP1 preserves hematopoietic stem cell potential under homeostasis and radiation-induced injury by alleviating ER stress [EMP1 RNA-seq]

Project description:Hematopoietic stem cells (HSCs) play a crucial role in lifelong hematopoiesis by generating all blood lineages. The long-term maintenance of HSCs relies on the regulation of endoplasmic reticulum (ER) stress at a low level. However, the precise control of ER stress in HSCs remains largely unknown. In this study, we demonstrate that suppression of ER stress enhances the in vitro maintenance and in vivo repopulation capacity of HSCs, while also protecting HSCs against radiation-induced injury. Integrated multi-omics analysis has revealed that epithelial membrane protein 1 (Emp1) functions as an ER stress sensor in HSCs. Loss of Emp1 leads to increased protein aggregates and elevated ER stress, ultimately resulting in impaired HSC maintenance and self-renewal. Mechanistically, EMP1 is located within the ER and interacts with ceramide synthase 2 (CERS2) to limit the production of dihydroceramides (dhCers), which are a class of sphingolipids. DhCers accumulate in Emp1-deficient HSCs and directly induce protein aggregation. Inhibition of CERS2 significantly restores the maintenance of Emp1-deficient HSCs. Furthermore, Emp1 deficiency renders HSCs more susceptible to radiation, while overexpression of Emp1 or inhibition of CERS2 protects HSCs against radiation-induced injury. These findings highlight the critical role played by the EMP1-CERS2-dhCers axis in constraining ER stress and preserving HSC potential, uncovering a new link between sphingolipid metabolism and HSC homeostasis, and have clinical implications.

2025-03-27 | GSE277442 | GEO

EMP1 preserves hematopoietic stem cell potential under homeostasis and radiation-induced injury by alleviating ER stress [ER-stress ATAC-seq]

2025-03-27 | GSE277444 | GEO

EMP1 preserves hematopoietic stem cell potential under homeostasis and radiation-induced injury by alleviating ER stress [ER-stress RNA-seq]

2025-03-27 | GSE277443 | GEO

EMP1 preserves hematopoietic stem cell potential under homeostasis and radiation-induced injury by alleviating ER stress

Project description:EMP1 preserves hematopoietic stem cell potential under homeostasis and radiation-induced injury by alleviating ER stress

| PRJNA1162428 | ENA

EMP1 preserves hematopoietic stem cell potential under homeostasis and radiation-induced injury by alleviating ER stress [EMP1 RNA-seq]

Project description:EMP1 preserves hematopoietic stem cell potential under homeostasis and radiation-induced injury by alleviating ER stress [EMP1 RNA-seq]

| PRJNA1162435 | ENA

EMP1 preserves hematopoietic stem cell potential under homeostasis and radiation-induced injury by alleviating ER stress [ER-stress RNA-seq]

Project description:EMP1 preserves hematopoietic stem cell potential under homeostasis and radiation-induced injury by alleviating ER stress [ER-stress RNA-seq]

| PRJNA1162431 | ENA

EMP1 preserves hematopoietic stem cell potential under homeostasis and radiation-induced injury by alleviating ER stress [ER-stress ATAC-seq]

Project description:EMP1 preserves hematopoietic stem cell potential under homeostasis and radiation-induced injury by alleviating ER stress [ER-stress ATAC-seq]

| PRJNA1162436 | ENA

Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homeostasis.

Project description:Hematopoietic stem cells (HSCs) balance self-renewal and differentiation to maintain hematopoietic fitness throughout life. In steady-state conditions, HSC exhaustion is prevented by the maintenance of most HSCs in a quiescent state, with cells entering the cell cycle only occasionally. HSC quiescence is regulated by retinoid and fatty-acid ligands of transcriptional factors of the nuclear retinoid X receptor (RXR) family. Herein, we show that dual deficiency for hematopoietic RXRα and RXRβ induces HSC exhaustion, myeloid cell/megakaryocyte differentiation, and myeloproliferative-like disease. RXRα and RXRβ maintain HSC quiescence, survival, and chromatin compaction; moreover, transcriptome changes in RXRα;RXRβ-deficient HSCs include premature acquisition of an aging-like HSC signature, MYC pathway upregulation, and RNA intron retention. Fitness loss and associated RNA transcriptome and splicing alterations in RXRα;RXRβ-deficient HSCs are prevented by Myc haploinsufficiency. Our study reveals the critical importance of RXRs for the maintenance of HSC fitness and their protection from premature aging.

| S-EPMC10082360 | biostudies-literature

Activation of SK2 channels preserves ER Ca²? homeostasis and protects against ER stress-induced cell death.

Project description:Alteration of endoplasmic reticulum (ER) Ca(2+) homeostasis leads to excessive cytosolic Ca(2+) accumulation and delayed neuronal cell death in acute and chronic neurodegenerative disorders. While our recent studies established a protective role for SK channels against excessive intracellular Ca(2+) accumulation, their functional role in the ER has not been elucidated yet. We show here that SK2 channels are present in ER membranes of neuronal HT-22 cells, and that positive pharmacological modulation of SK2 channels with CyPPA protects against cell death induced by the ER stressors brefeldin A and tunicamycin. Calcium imaging of HT-22 neurons revealed that elevated cytosolic Ca(2+) levels and decreased ER Ca(2+) load during sustained ER stress could be largely prevented by SK2 channel activation. Interestingly, SK2 channel activation reduced the amount of the unfolded protein response transcription factor ATF4, but further enhanced the induction of CHOP. Using siRNA approaches we confirmed a detrimental role for ATF4 in ER stress, whereas CHOP regulation was dispensable for both, brefeldin A toxicity and CyPPA-mediated protection. Cell death induced by blocking Ca(2+) influx into the ER with the SERCA inhibitor thapsigargin was not prevented by CyPPA. Blocking the K(+) efflux via K(+)/H(+) exchangers with quinine inhibited CyPPA-mediated neuroprotection, suggesting an essential role of proton uptake and K(+) release in the SK channel-mediated neuroprotection. Our data demonstrate that ER SK2 channel activation preserves ER Ca(2+) uptake and retention which determines cell survival in conditions where sustained ER stress contributes to progressive neuronal death.

| S-EPMC4832102 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data