Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Innate immune memory after brain injury drives inflammatory cardiac dysfunction

ABSTRACT: Besides the local inflammatory immune response in the brain, stroke also alters systemic immunity. Within the acute and sub-acute phase, the systemic immune response to stroke has been described in detail over last decades. The long-term systemic immunological consequences after stroke are however still elusive. Therefore, a better understanding of these long-lasting chronic effects of stroke on systemic immunity and its impact on remote organ function and secondary comorbidities is needed. Here, we used single-cell RNA sequencing (scRNA-Seq) to investigate the chronic effect of stroke on the transcriptomic signatures of resident myeloid immune cells in various peripheral organs remote from the brain, including the lung, heart, liver, spleen, blood and bone marrow. We observed that monocytes in peripheral organs and in the bone marrow adopt a pro-inflammatory phenotype which persists chronically after stroke. Moreover, the pro-inflammatory profile of monocytes in the bone marrow was transmissible by BM transplantation to naïve recipients, indicating potentially epigenetically imprinted chronic innate immune memory after stroke. Indeed, by performing single-nuclei ATAC sequencing, we found that post-stroke myeloid immune memory after stroke is likely mediated by IL-1b-driven mechanisms, and that neutralization of the post-stroke increase in circulating IL-1b prevented myeloid immune memory.

ORGANISM(S): Mus musculus

PROVIDER: GSE232098 | GEO | 2024/07/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Innate immune memory after brain injury drives inflammatory cardiac dysfunction [snATAC-seq]

Project description:Besides the local inflammatory immune response in the brain, stroke also alters systemic immunity. Within the acute and sub-acute phase, the systemic immune response to stroke has been described in detail over last decades. The long-term systemic immunological consequences after stroke are however still elusive. Therefore, a better understanding of these long-lasting chronic effects of stroke on systemic immunity and its impact on remote organ function and secondary comorbidities is needed. Here, we used single-cell RNA sequencing (scRNA-Seq) to investigate the chronic effect of stroke on the transcriptomic signatures of resident myeloid immune cells in various peripheral organs remote from the brain, including the lung, heart, liver, spleen, blood and bone marrow. We observed that monocytes in peripheral organs and in the bone marrow adopt a pro-inflammatory phenotype which persists chronically after stroke. Moreover, the pro-inflammatory profile of monocytes in the bone marrow was transmissible by BM transplantation to naïve recipients, indicating potentially epigenetically imprinted chronic innate immune memory after stroke. Indeed, by performing single-nuclei ATAC sequencing, we found that post-stroke myeloid immune memory after stroke is likely mediated by IL-1b-driven mechanisms, and that neutralization of the post-stroke increase in circulating IL-1b prevented myeloid immune memory.

2024-07-22 | GSE230692 | GEO

Innate immune memory after brain injury drives inflammatory cardiac dysfunction (cardiac interstitial cells)

2024-07-22 | GSE263035 | GEO

Innate immune memory after brain injury drives inflammatory cardiac dysfunction [bone marrow scRNA-Seq]

2024-07-22 | GSE262727 | GEO

Innate immune memory after brain injury drives inflammatory cardiac dysfunction [BMT2]

2024-07-22 | GSE262599 | GEO

Innate immune memory after brain injury drives inflammatory cardiac dysfunction [ATAC-Seq]

Project description:The enormous medical burden of stroke is not only due to the brain injury itself and the acute systemic effects, but is largely determined by chronic comorbidities that develop secondarily after stroke. We hypothesized that the high rate of comorbidity developing after a stroke might have a shared immunological cause, however, the chronic effects of brain injury on systemic immunity have so far been barely investigated. Here, we identified myeloid innate immune memory as a cause of remote organ dysfunction after stroke. Using single-cell sequencing, we identified persistent pro-inflammatory transcriptomic changes in resident monocytes/macrophages in multiple organs one month after experimental ischemic brain injury, which was particularly abundant in the heart and associated with the development of cardiac fibrosis and diastolic dysfunction. A similar phenotype was seen in myocardial autopsy samples from stroke versus control patients. We observed chronic functional changes in myeloid hematopoiesis driven by post-stroke IL-1-mediated epigenetic changes. These alterations could be transplanted to naïve recipient mice and were sufficient to induce cardiac dysfunction. By effectively blocking the trafficking of pro-inflammatory monocytes from the bone marrow to the heart using a dual CCR2/5 inhibitor, we successfully prevented post-stroke cardiac dysfunction. This approach holds promising potential as a novel immune-targeted secondary prevention therapy. We anticipate that the epigenetic immune reprogramming mechanisms detailed here for the brain-heart axis could be generalized to provide a novel framework for explaining the development of various comorbidities after acute tissue injury in remote organs.

2024-07-22 | GSE264093 | GEO

Innate immune memory after brain injury drives inflammatory cardiac dysfunction [CUT&tag]

2024-07-22 | GSE264418 | GEO

Innate immune memory after brain injury drives inflammatory cardiac dysfunction II

Project description:Besides the local inflammatory immune response in the brain, stroke also alters systemic immunity. Within the acute and sub-acute phase, the systemic immune response to stroke has been described in detail over last decades. The long-term systemic immunological consequences after stroke are however still elusive. Therefore, a better understanding of these long-lasting chronic effects of stroke on systemic immunity and its impact on remote organ function and secondary comorbidities is needed. Here, we investigated the long-term consequences of stroke on the heart. By performing serial cardiac ultrasound imaging in mice, we found that stroke leads to chronic cardiac dysfunction, which was associated with increased cardiac fibrosis. We found that this phenomenon was driven by an increased infiltration of bone marrow-derived monocytes into the heart after stroke, which results in increased expression of metalloproteinase-9 (Mmp9) by cardiac monocytes/macrophages. To further investigate the translational relevance of this post-stroke cardiac phenotype, we analyzed heart samples from patients who died due to stroke and control patients and performed bulk mRNA sequencing.

2024-07-22 | GSE232550 | GEO

The impact of remote solid tumors on bone marrow ecosystem at single-cell resolution

Project description:The bone marrow (BM) environment (BME) is inhabited by hematopoietic stem and progenitor cells (HSPCs) and niche cells, which are sources of bone homeostasis, hematopoiesis and immune response. The BM senses many pathological insults, including solid cancers. However, a comprehensive understanding of BM ecosystem response to solid cancer is lacking. Herein, by single-cell RNA sequencing, we characterized the BM landscape in tumor-bearing models prior to metastasis. We found that remote tumors induce dramatic systemic BM niche remodeling that drives HSPC reprogramming and dysfunctional hematopoiesis, which is distinct from innate immune responses.

2023-05-03 | GSE188648 | GEO

Sequence data for study: Mobilization of tissue-resident memory CD4+ T lymphocytes from bone marrow and their contribution to a systemic secondary immune reaction

Project description:Resident memory T lymphocytes (TRM) of epithelial tissues and the bone marrow protect their host tissue. To what extent these cells are mobilized and contribute to systemic immune reactions is less clear. Here we show that in secondary immune reactions to the measles-mumps-rubella (MMR) vaccine, CD4+ TRM are mobilized into the blood within 16 to 48 hours after immunization. This mobilization of TRM is cognate: TRM recognizing other antigens are not mobilized, unless they cross-react with the vaccine. We also demonstrate through methylome analyses that TRM are mobilized from the bone marrow. These mobilized cells make significant contribution to the systemic immune reaction, as evidenced by their T-cell receptor VÃŽÂ² clonotypes represented among the newly generated circulating memory T-cells, 14 days after vaccination. Thus, TRM of the bone marrow confer not only local, but also systemic immune memory.

| EGAS00001005475 | EGA

Adult skull bone marrow is an expanding and resilient hematopoietic reservoir

Project description:The bone marrow microenvironment is a critical regulator of hematopoietic stem cell self-renewal and fate. While it is appreciated that aging, chronic inflammation and other insults compromise bone marrow function and thereby negatively affect hematopoiesis, it is not known whether different bone compartments exhibit distinct microenvironmental properties and functional resilience. Here, we have employed imaging, pharmacological approaches, and mouse genetics to uncover specialized and highly surprising properties of bone marrow in adult and aging skull. Specifically, we show that the skull bone marrow undergoes lifelong expansion involving vascular growth, which results in an increasing contribution to total hematopoietic output. Furthermore, skull is largely protected against major hallmarks of aging, including upregulation of pro-inflammatory cytokines, adipogenesis and loss of vascular integrity. Striking dynamic and rapid changes to the skull vasculature and bone marrow are induced by physiological alterations, namely pregnancy, but also pathological challenges, such as stroke and experimental chronic myeloid leukemia. These responses are highly distinct from femur, the most extensively studied bone marrow compartment. We propose that skull harbors a protected and dynamically expanding bone marrow microenvironment, which is relevant for experimental studies but, potentially, also clinical treatments in humans.

2024-08-22 | GSE275179 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data