Mass‐Guided Single‐Cell MALDI Imaging of Low‐Mass Metabolites Reveals Cellular Activation Markers DOI Creative Commons
James L. Cairns,

Joan L. Huber,

Andrea Lewen

и другие.

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Дек. 12, 2024

Abstract Single‐cell MALDI mass spectrometry imaging (MSI) of lipids and metabolites >200 Da has recently come to the forefront biomedical research chemical biology. However, cell‐targeting metabolome‐preserving methods for analysis low mass, hydrophilic (<200 Da) in large cell populations are lacking. Here, PRISM‐MS ( PR escan I maging S mall M olecule – ass pectrometry) mass‐guided MSI workflow is presented, which enables space‐efficient single lipid metabolite analysis. In conjunction with giant unilamellar vesicles (GUVs) as ground truth cell‐sized objects Monte Carlo reference‐based consensus clustering data‐dependent identification subpopulations, on‐cell MS2‐based low‐mass like amino acids or Krebs cycle intermediates involved stimulus‐dependent activation. The utility demonstrated through characterization complex metabolome changes lipopolysaccharide (LPS)‐stimulated microglial cells human‐induced pluripotent stem cell‐derived microglia. Translation results endogenous microglia organotypic hippocampal slice cultures indicates that LPS‐activation involves itaconate‐to‐taurine ratio alterations neuron‐to‐glia glutamine‐glutamate shuttling. data suggests can serve a standard method metabolomics, given its capability characterize larger metabolites.

Язык: Английский

Microglial Responses to Alzheimer's Disease Pathology: Insights From “Omics” Studies DOI Open Access
Aquene N. Reid, Suman Jayadev, Katherine E. Prater

и другие.

Glia, Год журнала: 2025, Номер 73(3), С. 519 - 538

Опубликована: Янв. 6, 2025

Human genetics studies lent firm evidence that microglia are key to Alzheimer's disease (AD) pathogenesis over a decade ago following the identification of AD-associated genes expressed in microglia-specific manner. However, while alterations microglial morphology and gene expression observed human postmortem brain tissue, mechanisms by which drive contribute AD pathology remain ill-defined. Numerous mouse models have been developed facilitate disambiguation biological underlying AD, incorporating amyloidosis, phosphorylated tau, or both. Over time, use multiple technologies including bulk tissue single cell transcriptomics, epigenomics, spatial proteomics, lipidomics, metabolomics shed light on heterogeneity phenotypes molecular patterns altered models. Each these 'omics provide unique information insight. Here, we review literature approaches findings methods synthesis knowledge generated applying AD.

Язык: Английский

Процитировано

1
Role of Transcription Factor Fli-1 in Inflammation and Autoimmune Diseases DOI Creative Commons
Xuan Wang,

Xian K. Zhang

Biomolecules, Год журнала: 2025, Номер 15(4), С. 480 - 480

Опубликована: Март 25, 2025

Friend leukemia virus integration 1 (Fli-1), a member of the ETS family transcription factors, plays an essential role in diverse biological processes. Recent studies have underscored significance Fli-1 modulating inflammation and autoimmune diseases via regulation inflammatory responses. Specifically, exerts control over processes, influencing key effectors signaling pathways associated with conditions such as systemic lupus erythematosus, scleroderma, cancer, sepsis. This review aims to summarize emerging roles diseases, focus on elucidating underlying molecular mechanisms exploring potential therapeutic implications.

Язык: Английский

Процитировано

0
CMPK2 promotes microglial activation through the cGAS-STING pathway in the neuroinflammatory mechanism DOI Creative Commons
Feng Gao, Zijian Zheng, Xinjie Liu

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 7, 2025

The activation of microglia and the resulting neuroinflammation play crucial regulatory roles in pathogenesis progression neurological diseases, although specific mechanisms remain incompletely understood. Cytidine monophosphate kinase 2 (CMPK2) is a key mitochondrial nucleotide involved cellular energy metabolism synthesis. Recent studies suggest that CMPK2 plays role microglial-mediated neuroinflammation; however, its impact on microglial remains unclear. In this study, we hypothesize promotes by activating cGAS-STING signaling pathway. To investigate mechanism, employed lipopolysaccharide (LPS)-treated cells to detailed which regulates neuroinflammation. Our experimental results indicate BV2 mouse primary model, both protein transcript levels were significantly elevated, accompanied phenotypes such as increased cell size, shortened processes, transformation round or rod-like shapes, elevated CD40 expression. Concurrently, there was an increase pro-inflammatory cytokine decrease anti-inflammatory levels. Further investigation revealed microglial, expression cGAS STING along with oxidative products inflammatory responses. CMA stimulation further intensified these changes, while knockdown mitigated them. Finally, demonstrated inhibited stress, activation-related neuroinflammatory responses induced overexpression model. Molecular docking experiments showed stably binds at level. These findings pathway mediates CMPK2-induced activation. summary, our study demonstrates LPS-induced overactivity through

Язык: Английский

Процитировано

0
Neuroinflammation in Parkinson’s disease: focus on the relationship between miRNAs and microglia DOI Creative Commons
Ke Xu, Li Yan Yuan, Yan Zhou

и другие.

Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Июль 26, 2024

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder that affects the central nervous system (CNS). Neuroinflammation crucial factor in pathological advancement of PD. PD characterized by presence activated microglia and increased levels proinflammatory factors, which play role its pathology. During immune response PD, regulation significantly influenced microRNA (miRNA). The excessive activation microglia, persistent neuroinflammation, abnormal polarization macrophages brain can be attributed to dysregulation certain miRNAs. Additionally, there are miRNAs possess ability inhibit neuroinflammation. miRNAs, small non-coding epigenetic regulators, have modulate microglial activity both normal conditions. They also significant impact on promoting communication between neurons microglia.

Язык: Английский

Процитировано

3
Innate immunity—With an adaptive twist DOI
Steven Z. Josefowicz, Joseph C. Sun

Immunological Reviews, Год журнала: 2024, Номер 323(1), С. 5 - 7

Опубликована: Апрель 17, 2024

Язык: Английский

Процитировано

1
Epigenetic heterogeneity shapes the transcriptional landscape of regional microglia DOI Creative Commons
Alexander V. Margetts, Samara J. Vilca, Florence Bourgain-Guglielmetti

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 9, 2024

Abstract Microglia, the innate immune cells in central nervous system, exhibit distinct transcriptional profiles across brain regions that are important for facilitating their specialized function. There has been recent interest identifying epigenetic modifications associated with these profiles, as may improve our understanding of underlying mechanisms governing functional specialization microglia. One obstacle to achieving this goal is large number microglia required obtain a genome-wide profile single histone modification. Given cellular and regional heterogeneity brain, would require pooling many samples which impede biological applications limited by numbers available animals. To overcome obstacle, we have adapted method chromatin profiling known Cleavage Under Targets Tagmentation (CUT&Tag-Direct) differences gene expression throughout reward system. Consistent previous studies, find vary region. However, here report also network signatures specific each Additionally, region-dependent differential deposition H3K27ac H3K7me3, while H3K27me3 landscape remarkably stable regions, most consistent anatomical location explain profiles. Altogether, findings underscore established role cell fate determination support active dynamic regulation microglial expression. In study, molecular computational framework can be applied both health disease, using few 2,500 per mark. Figure 1. Pipeline tissue processing data analysis characterization transcriptome epigenome on scale.

Язык: Английский

Процитировано

1
Revolutionizing Neuroimmunology: Unraveling Immune Dynamics and Therapeutic Innovations in CNS Disorders DOI Open Access
Corneliu Toader,

Călin Petru Tătaru,

Octavian Munteanu

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(24), С. 13614 - 13614

Опубликована: Дек. 19, 2024

Neuroimmunology is reshaping the understanding of central nervous system (CNS), revealing it as an active immune organ rather than isolated structure. This review delves into unprecedented discoveries transforming field, including emerging roles microglia, astrocytes, and blood–brain barrier (BBB) in orchestrating neuroimmune dynamics. Highlighting their dual both repair disease progression, we uncover how these elements contribute to intricate pathophysiology neurodegenerative diseases, cerebrovascular conditions, CNS tumors. Novel insights microglial priming, astrocytic cytokine networks, meningeal lymphatics challenge conventional paradigms privilege, offering fresh perspectives on mechanisms. work introduces groundbreaking therapeutic innovations, from precision immunotherapies controlled modulation BBB using nanotechnology focused ultrasound. Moreover, explore fusion with neuromodulatory technologies, underscoring new frontiers for personalized medicine previously intractable diseases. By synthesizing advancements, propose a transformative framework that integrates cutting-edge research clinical translation, charting bold path toward redefining management era neuroimmunology.

Язык: Английский

Процитировано

1
Fast Single-Cell MALDI Imaging of Low-Mass Metabolites Reveals Cellular Activation Markers DOI Open Access
James L. Cairns,

Joan L. Huber,

Andrea Lewen

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 18, 2024

Abstract Single-cell MALDI mass spectrometry imaging (MSI) of lipids and metabolites >200 Da has recently come to the forefront biomedical research chemical biology, but fast metabolome-preserving methods without paraformaldehyde fixation for analysis low mass, hydrophilic (<200 Da) in large cell populations are lacking. Introducing giant unilamellar vesicles (GUVs) as MSI ground truth cell-sized objects Monte Carlo reference-based consensus clustering data-dependent identification subpopulations. The PRISM-MS ( PR escan I maging S mall M olecule - ass pectrometry) dual-scan workflow is presented, enabling space-efficient therefore faster lipid single GUVs cells. Beyond lipids, enables on-cell MS2-based low-mass like amino acids or Krebs cycle intermediates involved stimulus-dependent activation. utility demonstrated through characterization complex metabolome changes lipopolysaccharide (LPS)-stimulated microglial cells human-induced pluripotent stem cell-derived microglia. Translation results endogenous microglia organotypic hippocampal slice cultures indicates that LPS-activation involves itaconate-to-taurine ratio alterations neuron-to-glia glutamine-glutamate shuttling. data suggests could serve a standard method metabolomics, given its capability characterize larger metabolites.

Язык: Английский

Процитировано

0
Mass‐Guided Single‐Cell MALDI Imaging of Low‐Mass Metabolites Reveals Cellular Activation Markers DOI Creative Commons
James L. Cairns,

Joan L. Huber,

Andrea Lewen

и другие.

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Дек. 12, 2024

Abstract Single‐cell MALDI mass spectrometry imaging (MSI) of lipids and metabolites >200 Da has recently come to the forefront biomedical research chemical biology. However, cell‐targeting metabolome‐preserving methods for analysis low mass, hydrophilic (<200 Da) in large cell populations are lacking. Here, PRISM‐MS ( PR escan I maging S mall M olecule – ass pectrometry) mass‐guided MSI workflow is presented, which enables space‐efficient single lipid metabolite analysis. In conjunction with giant unilamellar vesicles (GUVs) as ground truth cell‐sized objects Monte Carlo reference‐based consensus clustering data‐dependent identification subpopulations, on‐cell MS2‐based low‐mass like amino acids or Krebs cycle intermediates involved stimulus‐dependent activation. The utility demonstrated through characterization complex metabolome changes lipopolysaccharide (LPS)‐stimulated microglial cells human‐induced pluripotent stem cell‐derived microglia. Translation results endogenous microglia organotypic hippocampal slice cultures indicates that LPS‐activation involves itaconate‐to‐taurine ratio alterations neuron‐to‐glia glutamine‐glutamate shuttling. data suggests can serve a standard method metabolomics, given its capability characterize larger metabolites.

Язык: Английский

Процитировано

0