Single cell transcriptome profiling of infrapatellar fat pad highlights the role of interstitial inflammatory fibroblasts in osteoarthritis

International Immunopharmacology, Год журнала: 2024, Номер 131, С. 111888 - 111888

Опубликована: Март 23, 2024

Osteoarthritis (OA) is a whole-joint disease in which the role of infrapatellar fat pad (IFP) its pathogenesis unclear. Our study explored cellular heterogeneity IFP to understand OA and identify therapeutic targets. Single-cell single-nuclei RNA sequencing were used analyze 10 samples, comprising 5 from patients healthy controls. Analyses included differential gene expression, enrichment, pseudotime trajectory, communication, along with comparative studies visceral subcutaneous fats. Key subcluster pathways validated using multiplex immunohistochemistry. The scRNA-seq performed on IFPs control group profiled expressions over 49,674 cells belonging 11 major cell types. We discovered that adipose stem progenitor (ASPCs), contributing formation both adipocytes synovial-lining fibroblasts (SLF). Interstitial inflammatory (iiFBs) ASPCs exhibit notable pro-inflammatory proliferative characteristics. identified four adipocyte subtypes, one subtype showing reduced lipid synthesis ability. Furthermore, iiFBs modulated activities macrophages T IFP. Compared tissues, represented distinctive subpopulation regulated cartilage proliferation through MK pathway. This presents comprehensive single-cell transcriptomic atlas IFP, uncovering complex landscape potential impact progression. findings highlight OA, especially pathway, opening new avenues for understanding developing novel targeted therapies.

Язык: Английский

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Extracellular vesicles from mouse trophoblast cells: Effects on neural progenitor cells and potential participants in the placenta–brain axis

Biology of Reproduction, Год журнала: 2023, Номер 110(2), С. 310 - 328

Опубликована: Окт. 26, 2023

Abstract The fetal brain of the mouse is thought to be dependent upon placenta as a source serotonin (5-hydroxytryptamine; 5-HT) and other factors. How factors reach developing remains uncertain but are postulated here part cargo carried by placental extracellular vesicles (EV). We have analyzed protein, catecholamine, small RNA content EV from trophoblast stem cells (TSC) TSC differentiated into parietal giant (pTGC), potential primary purveyors 5-HT. Current studies examined how exposure neural progenitor (NPC) either or pTGC affect their transcriptome profiles. contained relatively high amounts 5-HT, well dopamine norepinephrine, there were no significant differences between derived TSC. Content miRNA nucleolar (sno)RNA, however, did differ according source, snoRNA upregulated in pTGC. inferred targets microRNA (miRNA) both mRNA enriched brain. NPC readily internalized EV, leading changes Transcripts regulated mainly ones tissues. transcripts EV-treated that demonstrated likely complementarity with up- rather than downregulated, functions linked neuronal processes. Our results consistent placenta-derived providing direct support for development being an integral placenta–brain axis.

Язык: Английский

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Functional diversities within neurons and astrocytes in the adult rat auditory cortex revealed by single-nucleus RNA sequencing

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

Опубликована: Апрель 20, 2024

Abstract The mammalian cerebral cortex is composed of a rich diversity cell types. Cortical cells are organized into networks that rely on their functional to ultimately carry out variety sophisticated cognitive functions. To investigate the breadth transcriptional diverse types in sensory cortex, we have used single-nucleus RNA sequencing (snRNA-seq) auditory adult rat. A unique excitatory and inhibitory neuron were identified. In addition, report for first time astrocytes may represent functionally subtypes. Together, these results pave way building models how neurons work concert with at synapses fulfill high-cognitive functions like learning memory.

Язык: Английский

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Astrocytes remember inflammation

Immunity, Год журнала: 2024, Номер 57(5), С. 938 - 940

Опубликована: Май 1, 2024

Язык: Английский

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Histone H3 serotonylation dynamics in dorsal raphe nucleus contribute to stress- and antidepressant-mediated gene expression and behavior

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Май 4, 2023

ABSTRACT Background Major depressive disorder (MDD), along with related mood disorders, is a debilitating illness that affects millions of individuals worldwide. While chronic stress increases incidence levels stress-mediated disruptions in brain function precipitate these illnesses remain elusive. Serotonin-associated antidepressants (ADs) the first line therapy for many symptoms, yet low remission rates and delays between treatment symptomatic alleviation have prompted skepticism regarding precise roles serotonin precipitation disorders. Our group recently demonstrated epigenetically modifies histone proteins (H3K4me3Q5ser) to regulate transcriptional permissiveness brain. However, this phenomenon has not been explored following and/or AD exposures. Methods We employed combination genome-wide biochemical analyses dorsal raphe nucleus (DRN) male female mice exposed social defeat examine impact exposures on H3K4me3Q5ser dynamics, as well associations mark stress-induced gene expression. additionally assessed regulation exposures, viral-mediated reduce DRN stress-associated expression behavior. Results found plays important plasticity. Chronically stressed displayed dysregulated dynamics DRN, both AD- disruption proving sufficient rescue Conclusions These findings establish neurotransmission-independent role stress-/AD-associated behavioral plasticity DRN.

Язык: Английский

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