Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Peripheral human red blood cell development in human immune system (HIS) mouse model with heme oxygenase-1 (HMOX-1) deficiency

ABSTRACT: A challenge for human immune system (HIS) mouse models has been the lack of human red blood cells (hRBCs) survival after engraftment of these immune-deficient mice with human CD34+ hematopoietic stem cells (HSCs). Even though human white blood cells can develop in the peripheral blood of these human HSC-engrafted mice, and human erythroid progenitors are found in the murine bone marrow (BM), the hRBCs are quickly phagocytosed by murine macrophages upon egress from the BM. The challenge is further exacerbated by the pathology in BM development that occurs upon complete genetic ablation of murine myeloid cells, rendering such an approach impractical. Heme oxygenase-1 (HMOX-1) deficient mice have reduced macrophages due to toxic build-up of intracellular heme upon engulfment of red blood cells, but do not have an overall loss of myeloid cells. We took advantage of this observation and generated a HMOX-1-/- on a humanized M-CSF/SIRPa/CD47 Rag2-/- IL-2Ryc-/- background. These mice have reduced murine macrophages but comparable level of murine myeloid cells to HMOX-1+/+ control mice in the same background. Injected hRBCs survive longer in HMOX-1-/- mice than in HMOX-1+/+ controls. Since hRBC are present in the peripheral blood of engrafted HMOX-1-/- mice, these mice have the potential to be used for hematological disease modeling, and to test therapeutic treatments for hRBC diseases in vivo.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE239736 | GEO | 2023/08/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Profound Immune Alterations in the Murine CML Bone Marrow Microenvironment Revealed by Single Cell Ph- Macrophage Profiling and Secretory Proteomics

Project description:Macrophages are cells of the innate immune system fundamental to support normal haematopoiesis, fight infection, anti-cancer immunity and tumour progression. However, the function of macrophages in myeloid leukaemias remain largely unknown, due to difficulties in isolating non-transformed cells from the malignant ones. Here we use a state-of-the-art chimeric mouse of chronic myeloid leukaemia (CML) to study in the impact of the dysregulated bone marrow (BM) microenvironment on bystander macrophages. Utilising single cell RNA sequencing (scRNA seq) of Philadelphia chromosome (Ph) negative macrophages and secretome proteomics of murine c-kit+ stem/progenitor cells we have uncovered that macrophages exposed to a CML environment are altered transcriptionally and have reduced phagocytic function

2023-12-23 | PXD022366 | Pride

Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge (ATAC-Seq)

Project description:Microglia are yolk sac-derived macrophages residing in the parenchyma of brain and spinal cord, where they interact with neurons and other glial cells by constantly probing their surroundings with dynamic extensions. After different conditioning paradigms and bone marrow (BM) or hematopoietic stem cell (HSC) transplantation, graft-derived cells seed the brain and persistently contribute to the parenchymal brain macrophage compartment. Here we establish that graft-derived macrophages acquire, over time, microglia characteristics, including ramified morphology, longevity, radio-resistance and clonal expansion. However, even after prolonged CNS residence, transcriptomes and chromatin accessibility landscapes of engrafted, BM-derived macrophages remain distinct from yolk sac-derived host microglia. Furthermore, engrafted BM-derived cells display discrete responses to peripheral endotoxin challenge, as compared to host microglia. In human HSC transplant recipients, engrafted cells also remain distinct from host microglia, extending our finding to clinical settings. Collectively, our data emphasize the molecular and functional heterogeneity of parenchymal brain macrophages and highlight potential clinical implications for HSC gene therapies aimed to ameliorate lysosomal storage disorders, microgliopathies or general monogenic immuno-deficiencies.

2018-11-21 | GSE122768 | GEO

Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge (RNA-Seq)

2018-11-21 | GSE122766 | GEO

Distinct metabolic responses to heme in inflammatory human and mouse macrophages - Role of nitric oxide

Project description:Activation of inflammation is tightly associated with metabolic reprogramming in macrophages. The iron-containing tetrapyrrole heme can induce pro-oxidant and pro-inflammatory effects in murine macrophages, but has been associated with polarization towards an anti-inflammatory phenotype in human macrophages. In the current study, we compared the regulatory responses to heme and the prototypical Toll-like receptor (TLR)4 ligand lipopolysaccharide (LPS) in human and mouse macrophages with a particular focus on alterations of cellular bioenergetics. In human macrophages, bulk RNA-sequencing analysis indicated that heme led to an anti-inflammatory transcriptional profile, whereas LPS induced a classical pro-inflammatory gene response. Co-stimulation of heme with LPS caused opposing regulatory patterns of inflammatory activation and cellular bioenergetics in human and mouse macrophages. Specifically, in LPS-stimulated murine, but not human macrophages, heme led to a marked suppression of oxidative phosphorylation and an up-regulation of glycolysis. The species-specific alterations in cellular bioenergetics and inflammatory responses to heme were critically dependent on the availability of nitric oxide (NO) that is generated in inflammatory mouse, but not human macrophages. Accordingly, studies with an inducible nitric oxide synthase (iNOS) inhibitor in mouse, and a pharmacological NO donor in human macrophages, reveal that NO is responsible for the opposing effects of heme in these cells. Taken together, the current findings indicate that NO is critical for the immunomodulatory role of heme in macrophages.

2024-05-13 | GSE255234 | GEO

Gene expression profile at the single cell level of CD45+ CD11b+ cells isolated from the brain and bone marrow of mice either untreated or conditioned and transplanted with total bone marrow.

Project description:We used single-cell RNA sequencing (scRNA-seq) to analyze the diversity of bone marrow-derived CD45+CD11b+ microglia-like cells (MGLCs) engrafted in the brain of recipient mice that were conditioned using Busulfan and PLX3397 and transplanted with total bone marrow. We compared the gene expression of MGLCs to that of developmentally-derived CD45+ CD11b+ microglia/myeloid cells isolated from the brain of recipient mice (host microglia) and untreated mice (naive microglia). We also compared the gene expression of MGLCs to that of transplant-derived CD45+ CD11b+ cells engrafted in the bone marrow (abbreviated as BM-CD11b+)

2024-05-13 | GSE241877 | GEO

Heme-Nrf2 signaling shifts myeloid differentiation

Project description:Heme is an erythrocyte-derived toxin that drives disease progression in hemolytic anemias. During hemolysis, specialized bone marrow-derived macrophages with a high heme-metabolism capacity orchestrate disease adaptation by removing damaged erythrocytes and heme-protein complexes from the blood and supporting iron recycling for erythropoiesis. Here, we performed single-cell RNA sequencing with RNA velocity analysis of GM-CSF-supplemented mouse bone marrow cultures to assess myeloid differentiation under heme stress. We found that heme-activated NRF2 signaling shifted the differentiation trajectories of cells towards antioxidant, iron-recycling macrophages at the expense of dendritic cells, as these cells were selectively deficient in heme-exposed bone marrow cultures. Heme eliminated the capacity of GM-CSF-supplemented bone marrow cultures to activate antigen-specific T cells. The generation of functionally competent dendritic cells was restored by NRF2 loss. The heme-induced phenotype was reproduced in hemolytic mice with sickle cell disease and spherocytosis and associated with reduced dendritic cell functions in the spleen. Our data provide a novel mechanistic underpinning how hemolytic stress may provoke hyposplenism-related secondary immunodeficiency, which is a critical determinant of mortality in patients with genetic hemolytic anemias.

2022-01-25 | GSE179359 | GEO

Deviated myeloid differentiation in SCD mice under heme stress II.

2022-01-25 | GSE179364 | GEO

Deviated myeloid differentiation in SCD mice under heme stress I.

2022-01-25 | GSE179363 | GEO

Heme exposure shifts shifts myeloid differentiation in bone marrow derived mixed cell cultures.

2022-01-25 | GSE179362 | GEO

Heme signaling shifts myeloid differentiation in GM-CSF BM cell cultures

2022-01-25 | GSE179360 | GEO