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

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

PROVIDER: PRJNA1162428 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30709700_1.fastq.gz	Fastqsanger.gz
	SRR30709700_2.fastq.gz	Fastqsanger.gz
	SRR30709805_1.fastq.gz	Fastqsanger.gz
	SRR30709805_2.fastq.gz	Fastqsanger.gz
	SRR30709806_1.fastq.gz	Fastqsanger.gz

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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 RNA-seq]

2025-03-27 | GSE277443 | 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 [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 ATAC-seq]

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

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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]

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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.

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

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

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Autophagy controls mucus secretion from intestinal goblet cells by alleviating ER stress super

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Project description:ADAR1-Dependent RNA Editing Promotes MET and iPSC Reprogramming by Alleviating ER Stress

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