Age-induced alterations of granulopoiesis generate atypical neutrophils that aggravate stroke pathology. [scRNA-Seq 2]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE231822 | GEO | 2023/05/16
REPOSITORIES: GEO
Similar Datasets
Project description:Stroke in aging leads to a dysregulated emergency granulopoiesis impacting neurological outcome.
2023-05-16 | GSE174439 | GEO
Project description:Functional analysis demonstrates that neutrophils generated by emergency granulopoiesis have elevated bactericidal activity when compared to control (steady state) neutrophils. To determine if transcriptomic changes support these functional adaptations, we performed gene expression analysis on emergency granulopoiesis and steady state neutrophils before and after infection.
2023-05-01 | GSE217064 | GEO
Project description:Emergency granulopoiesis refers to the increased production of neutrophils in bone marrow and their release into circulation induced by severe infection. Several studies point to a critical role for granulocyte colony-stimulating factor (G-CSF) as the main mediator of emergency granulopoiesis. However, the consequences of G-CSF stimulation on the transcriptome of neutrophils and their precursors have not yet been investigated in humans. Here, we examine the changes in mRNA expression induced by administration of G-CSF in vivo, as a model of emergency granulopoiesis in humans. Blood samples were collected from healthy individuals after five days of G-CSF administration. Neutrophil precursors were sorted into discrete stages of maturation by flow cytometry, and RNA was subjected to microarray analysis. mRNA levels were compared to previously published expression levels in corresponding populations of neutrophil precursors isolated from bone marrow of untreated, healthy individuals. 1110 mRNAs were differentially expressed more than 2-fold throughout terminal granulopoiesis. Major changes were seen in pathways involved in apoptosis, cytokine signaling, and Toll-like receptor pathways. In addition, G-CSF treatment reduced the levels of four out of five measured granule proteins in mature neutrophils including the proantibacterial protein hCAP-18, which was completely deficient in neutrophils from G-CSF-treated donors. These results indicate that multiple biological processes are altered in order to satisfy the increased demand for neutrophils during G-CSF-induced emergency granulopoiesis in humans.
2017-04-04 | E-MTAB-4668 | biostudies-arrayexpress
Project description:Ischemic stroke is one of the leading causes of disability and mortality worldwide, recognizing aging as a prominent risk factor and determinant of dismal outcome. Aging is known to lead to overall frailty due to multifactorial changes, but pathogenic mechanisms underlying poor outcome remain unclear. Here we show that deterioration in elderly stroke is preceded by neutrophil accumulation and clogging in the ischemic brain microcirculation leading to a worse no-reflow phenomenon. With high-dimensional single-cell profiling over time of the brain's, blood's, and bone marrow's immune response, we could delineate after stroke four main neutrophil clusters in the blood whose quantitative and temporal dynamic of release is deranged in the bone marrow of the old. In the elderly, stroke triggers an early surge in the blood of the CD62Llo neutrophil subset characterized by a signature of bone marrow proximity, senescence, and oxidative stress. Functionally, transfer of this neutrophil subset displaying prominent thrombogenic features in young stroke mice leads to increased clogging of the ischemic brain microcirculation, worse no-reflow and outcome. Interrogating the blood leukocyte landscape of a large human stroke cohort with extensive single-cell proteome analyses, we confirmed that older stroke patients display a similar precocious accumulation of blood CD62Llo neutrophil subset, worse reperfusion and outcome. Our results demonstrate how age-related alterations in the process of neutrophil differentiation and release from the bone marrow have a relevant pathogenic role in the major cerebrovascular disorder affecting the world population, that unleash emergency granulopoiesis.
2023-05-16 | GSE174438 | GEO
Project description:To understand whether hematopoietic stem cells (HSCs) take part in emergency granulopoiesis, WT C57BL6 mice were treated intraperitoneally with 35 ug of LPS (lipopolysacharide) to induce emergency granulopoiesis or PBS control. Mice were sacrificed 4 hours after the treatment andHSCs (Lin-c-Kit+Sca-1+CD48-CD150+) were sorted and subjected to scRNA-seq.
2023-10-16 | E-MTAB-12324 | biostudies-arrayexpress
Project description:To understand whether hematopoietic stem cells (HSCs) take part in emergency granulopoiesis, WT C57BL6 mice were treated intraperitoneally with 35 ug of lipopolysacharide (LPS) to induce emergency granulopoiesis, or PBS control. Mice were sacrificed 4 hours after the treatment and HSCs (Lin-c-Kit+Sca-1+CD48-CD150+) were sorted and subjected to bulk ATACseq.
2023-10-16 | E-MTAB-12310 | biostudies-arrayexpress
Project description:The erythroblastic island (EBI), composed of a central macrophage and surrounding maturing erythroblasts, is the erythroid precursor niche. Despite numerous studies, its precise composition is still unclear. Using multispectral imaging flow cytometry (IFC), in vitro island reconstitution, and single cell RNA-seq of EBI-component cells enriched by gradient sedimentation, we present evidence that CD11b+ cells present in the EBIs are neutrophil precursors specifically associated with bone marrow EBI macrophages, indicating that erythro-(myelo)-blastic islands are a site for terminal granulopoiesis as well as erythropoiesis and production of these lineages is dynamically regulated within this niche. We further demonstrate that the balance between these lineages is determined by pathophysiological conditions, favoring granulopoiesis during anemia of inflammation, or erythropoiesis after erythropoietin (Epo) stimulation. Finally, we provide the heterogeneous molecular profiling of EBI macrophages as revealed by Cellular Indexing of Transcriptome and Epitopes (CITE)-sequencing of mouse bone marrow EBIs at baseline and after Epo-stimulation in vivo. Altogether, these data demonstrate that EBIs serve a dual role as terminal erythropoiesis and granulopoiesis niches and the central macrophages adapt to the needs of stress erythropoiesis as well as granulopoiesis.
2022-07-22 | GSE196347 | GEO
Project description:To address whether ELF-MF influences the epigenetic landscape in differentiating haematopoietic cells, we performed an in vitro haematopoietic differentiation under powerline-simulating ELF-MF exposure (50 Hz, 1 mT, 5’ on/10’ off) in comparison to sham exposure (50 Hz, 7 µT, 5’ on/10’ off) or no exposure. We differentiated CD34+ cells (allcells, CB008F, lot: CBC121009M) isolated from human cord blood into the neutrophilic lineage, and performed genome-wide methylation analysis at single CpG sites of CD34+ cells and day 5 progenitors, using the Illumina Infinium HumanMethylation 450 platform. Exposure to ELF MF did not significantly impact the programming of DNA methylation pattern during granulopoiesis. However, ELF MF exposure has an influence on the robustness of the epigenetic landscape during global chromatin programming of granulopoiesis. Our data suggests that ELF MF has a stochastic effect on the epigenetic landscape of individual cells.
2017-06-13 | GSE85392 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-05-16 | GSE174440 | GEO
Project description:The study investigated the changes in DNA-methylation and gene expression during granulopoiesis. To this end CMP, GMP, PMC and PMN cell populations were isolated by FACS from bone marrow from healthy donors and analysed by CAGE as well as expression and DNA microarrays.
2014-03-27 | GSE50797 | GEO