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Long-term effects of low doses of γ-irradiation on hematopoietic stem cells

ABSTRACT: Analysis of highly purified long-term hematopoietic stem cells (LT-HSCs) irradiated at 0Gy, 0.02Gy, 0.1Gy and 0.5Gy six months after transplantation. Results provide insight into the molecular mechanisms underlying multiple aspects of LT-HSCs premature ageing after low doses of γ-irradiation (0.02Gy).

ORGANISM(S): Mus musculus

PROVIDER: GSE66375 | GEO | 2016/02/26

SECONDARY ACCESSION(S): PRJNA277063

REPOSITORIES: GEO

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Long-term effects of low doses of Î³-irradiation on hematopoietic stem cells

Project description:Analysis of highly purified long-term hematopoietic stem cells (LT-HSCs) irradiated at 0Gy, 0.02Gy, 0.1Gy and 0.5Gy six months after transplantation. Results provide insight into the molecular mechanisms underlying multiple aspects of LT-HSCs premature ageing after low doses of Î³-irradiation (0.02Gy). Four samples were analyzed and correlated with the control group (0Gy).

2016-02-26 | E-GEOD-66375 | biostudies-arrayexpress

Immediate response of hematopoietic stem cells to low doses of γ-irradiation

Project description:Analysis of highly purified long-term hematopoietic stem cells (LT-HSCs) 2 hours after irradiation at 0Gy, 0.02Gy and 2.5Gy. Results provide insight into the molecular mechanisms underlying LT-HSCs immediate response to low doses of γ-irradiation compared to high doses.

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Immediate response of hematopoietic stem cells to low doses of Î³-irradiation

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Project description:Hematopoietic stem cells (HSCs) self-renew and generate all blood cells. Recent studies with single-cell transplants and lineage tracing suggest that adult HSCs are diverse in their reconstitution and lineage potentials. However, prospective isolation of these subpopulations has remained challenging. Here, we identify Neogenin-1 (NEO1) as a unique surface marker on a fraction of mouse HSCs labeled with Hoxb5, a specific reporter of long-term HSCs (LT-HSCs). We show that NEO1+Hoxb5+ LT-HSCs expand with age and respond to myeloablative stress in young mice, while NEO1–Hoxb5+ LT-HSCs exhibit no significant change in number. Furthermore, NEO1+Hoxb5+ LT-HSCs are more often in the G2/S cell cycle phase compared to NEO1–Hoxb5+ LT-HSCs in both young and old bone marrow. Upon serial transplantation, NEO1+Hoxb5+ LT-HSCs exhibit myeloid-biased differentiation and reduced reconstitution, while NEO1–Hoxb5+ LT-HSCs are lineage-balanced and stably reconstitute recipients. Gene expression analysis reveals erythroid and myeloid priming in the NEO1+ fraction and association of quiescence and self-renewal-related transcription factors with NEO1− LT-HSCs. Finally, transplanted NEO1+Hoxb5+ LT-HSCs rarely generate NEO1–Hoxb5+ LT-HSCs, while NEO1–Hoxb5+ LT-HSCs repopulate both LT-HSC fractions. This supports a model in which dormant, balanced, NEO1–Hoxb5+ LT-HSCs can hierarchically precede active, myeloid-biased NEO1+Hoxb5+ LT-HSCs.

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Methylomic analysis identifies the involvement of migration and adhesion genes in the ageing of primary haematopoietic stem cells

Project description:we utilize Nano-MeDIP-seq for the analysis of the LT-HSC methylome and, for the first time, simultaneously interrogate the methylome and transcriptome of a homogeneous population of primary murine HSCs, in order to define the underlying causes of changes in HSC functionality during normal ageing. We isolated and phenotyped primary LT-HSCs from young, middle-aged and old mice and subjected them to comprehensive methylome (MeDIP-seq) and transcriptome (RNA-seq) analysis.

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Immediate and long-term effects of low doses of γ-irradiation on hematopoietic stem cells

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

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Next Generation Sequencing of long-term hematopoietic cells (LT-HSCs) with or without mutations in JAK2 and Ezh2

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2016-06-24 | E-GEOD-82073 | biostudies-arrayexpress

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