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Mitochondrial Potentiation Ameliorates Age Related Heterogeneity in Hematopoietic Stem Cell Function [HSCs treated]

ABSTRACT: Mitochondrial Potentiation Ameliorates Age Related Heterogeneity in Hematopoietic Stem Cell Function [HSCs treated]

PROVIDER: PRJNA659054 | ENA |

REPOSITORIES: ENA

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Mitochondrial Potentiation Ameliorates Age Related Heterogeneity in Hematopoietic Stem Cell Function [HSCs treated]

Project description:introduction: Ageing is associated with reduced fitness and increased myeloid bias of the hematopoietic stem cell (HSC) compartment, causing increased risk of immune compromise, anemia and malignancy results: We show that mitochondrial membrane potential (MMP) can be used to prospectively isolate chronologically old HSCs with transcriptional features and functional attributes characteristic of young HSCs, including a high rate of transcription and balanced lineage-affiliated programmes. Strikingly, MMP is a stronger determinant of the quantitative and qualitative transcriptional state of HSCs than chronological age and transcriptional consequences of manipulation of MMP in HSCs within their native niche suggest a causal relationship. Accordingly, we show that pharmacological enhancement of MMP in old HSCs in vivo increases engraftment potential upon transplantation and reverses myeloid-biased peripheral blood output at steady state. conclusion: Our results demonstrate that MMP is a source of heterogeneity in old HSCs and its pharmacological manipulation can alter transcriptional programs with beneficial consequences for function.

2020-10-19 | GSE156807 | GEO

Mitochondrial Potentiation Ameliorates Age Related Heterogeneity in Hematopoietic Stem Cell Function [MMPhigh and MMPlow HSCs]

Project description:Mitochondrial Potentiation Ameliorates Age Related Heterogeneity in Hematopoietic Stem Cell Function [MMPhigh and MMPlow HSCs]

| PRJNA659051 | ENA

Mitochondrial Potentiation Ameliorates Age Related Heterogeneity in Hematopoietic Stem Cell Function [MMPhigh and MMPlow HSCs]

2020-10-19 | GSE156805 | GEO

Mitochondrial Potentiation Ameliorates Age Related Heterogeneity in Hematopoietic Stem Cell Function

Project description:Mitochondrial Potentiation Ameliorates Age Related Heterogeneity in Hematopoietic Stem Cell Function

| PRJNA659055 | ENA

Mitochondrial Potentiation Ameliorates Age Related Heterogeneity in Hematopoietic Stem Cell Function

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

2020-10-19 | GSE156808 | GEO

Mutant ASXL1 induces age-related expansion of phenotypic hematopoietic stem cells through activation of Akt/mTOR pathway

Project description:Somatic mutations of ASXL1 are frequently detected in age-related clonal hematopoiesis (CH). However, how ASXL1 mutations drive CH remains elusive. Using knockin (KI) mice expressing a C-terminally truncated form of ASXL1-mutant (ASXL1-MT), we examined the influence of ASXL1-MT on physiological aging in hematopoietic stem cells (HSCs). HSCs expressing ASXL1-MT display competitive disadvantage after transplantation. Nevertheless, in genetic mosaic mouse model, they acquire clonal advantage during aging, recapitulating CH in humans. Mechanistically, ASXL1-MT cooperates with BAP1 to deubiquitinate and activate AKT. Overactive Akt/mTOR signaling induced by ASXL1-MT results in aberrant proliferation and dysfunction of HSCs associated with age-related accumulation of DNA damage. Treatment with an mTOR inhibitor rapamycin ameliorates aberrant expansion of the HSC compartment as well as dysregulated hematopoiesis in aged ASXL1-MT KI mice. Our findings suggest that ASXL1-MT provokes dysfunction of HSCs, whereas it confers clonal advantage on HSCs over time, leading to the development of CH.

2021-02-08 | MSV000086816 | MassIVE

Mitochondrial respiratory chain is essential for hematopoietic stem cell function

Project description:Adult and fetal hematopoietic stem cells (HSCs) display a glycolytic phenotype, which is required for maintenance of stemness; however, whether mitochondrial respiration is required to maintain HSC function is not known. Here we report that loss of the mitochondrial complex III subunit Rieske iron sulfur protein (RISP) in fetal mouse HSCs allows them to proliferate but impairs their differentiation, resulting in anemia and prenatal death. RISP null fetal HSCs displayed impaired respiration resulting in a decreased NAD+/NADH ratio. RISP null fetal HSCs and progenitors exhibited an increase in both DNA and histone methylation concomitant with increases in 2-hydroxyglutarate (2-HG), a metabolite known to inhibit DNA and histone demethylases. RISP inactivation in adult HSCs also impaired respiration resulting in loss of quiescence resulting in severe pancytopenia and lethality. Thus, respiration is dispensable for adult or fetal HSC proliferation, but essential for fetal HSC differentiation and maintenance of adult HSC quiescence.

2017-09-13 | PXD006054 | Pride

Hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs)

Project description:Transcriptional profiling of hematopoietic stem and progenitor cells comparing Bmi1 KO HSCs and MPPs to WT HSCs and MPPs

2021-09-27 | GSE184739 | GEO

Analysis of differentially expressed genes in murine Satb1-deficient hematopoietic stem cells (HSCs) compared to wild-type HSCs

Project description:Gene expression analysis on purified murine hematopoietic stem cells (HSCs) deficient for Special AT-rich sequence-binding protein 1 (Satb1) compared to wild-type HSCs. Analysis of gene expression of bone marrow-derived CD45.2+ CD150+cKit+Sca-1+CD4-CD8a-CD19-B220-Gr-1- HSCs from congenic recipient animals transplanted >20 weeks with either wild-type or Satb1-deficient hematopoeitic cells.

2013-04-07 | E-GEOD-44107 | biostudies-arrayexpress

Analysis of differentially expressed genes in murine Satb1-deficient hematopoietic stem cells (HSCs) compared to wild-type HSCs

Project description:Gene expression analysis on purified murine hematopoietic stem cells (HSCs) deficient for Special AT-rich sequence-binding protein 1 (Satb1) compared to wild-type HSCs.

2013-04-07 | GSE44107 | GEO

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