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Stress-induced hematopoietic failure in the absence of immediate early response gene X-1 (IEX-1, IER3).

ABSTRACT: Expression of the immediate early response gene X-1 (IEX-1, IER3) is diminished significantly in hematopoietic stem cells in a subgroup of patients with early stage myelodysplastic syndromes, but it is not clear whether the deregulation contributes to the disease. The current study demonstrates increased apoptosis and a concomitant decrease in the number of hematopoietic stem cells lacking this early response gene. Null mutation of the gene also impeded platelet differentiation and shortened a lifespan of red blood cells. When bone marrow cells deficient in the gene were transplanted into wild-type mice, the deficient stem cells produced significantly fewer circulating platelets and red blood cells, despite their enhanced repopulation capability. Moreover, after exposure to a non-myeloablative dose of radiation, absence of the gene predisposed to thrombocytopenia, a significant decline in red blood cells, and dysplastic bone marrow morphology, typical characteristics of myelodysplastic syndromes. These findings highlight a previously unappreciated role for this early response gene in multiple differentiation steps within hematopoiesis, including thrombopoiesis, erythropoiesis and in the regulation of hematopoietic stem cell quiescence. The deficient mice offer a novel model for studying the initiation and progression of myelodysplastic syndromes as well as strategies to prevent this disorder.

SUBMITTER: Ramsey H

PROVIDER: S-EPMC3912958 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Immediate Early Response Gene X-1 (IEX-1) Mediates Ischemic Preconditioning-Induced Cardioprotection in Rats.

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IER3 (IEX-1) dysregulation serves as a potential prognostic factor in acute myeloid leukemia patients.

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Rearrangements and amplification of IER3 (IEX-1) represent a novel and recurrent molecular abnormality in myelodysplastic syndromes.

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

2023-05-04 | GSE231521 | GEO

Ttc7a regulates hematopoietic stem cell functions while controlling the stress-induced response.

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Stress-induced splicing activation of immediate early genes by nuclear speckle reorganization [ThioU]

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