Neuronal signal-regulatory protein alpha drives microglial phagocytosis by limiting microglial interaction with CD47 in the retina

Jiang, Danye; Burger, Courtney A.; Akhanov, Viktor; Liang, Justine H; Mackin, Robert; Albrecht, Nicholas E.; Andrade, Pilar; Schafer, Dorothy P.; Samuel, Melanie A.

doi:10.1016/j.immuni.2022.10.018

Cited by 31 publications

(12 citation statements)

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“…We conducted further analysis on the integrated single-cell transcriptome data to identify cluster-specific markers. Our results indicate that chicken basilar papilla HCs express the specific marker CALB1 (Jiang et al, 2022), while lagena and utricle HCs express CALB2 (Kawai et al, 2021) (Figure 9b,c). To confirm these findings, we used immunofluorescence and verified the expression of CALB2 protein in HCs in both the lagena and utricle and the expression of CALB1 protein in basilar papilla HCs (Figure 9d).…”

Section: Integration Of Scrna-seq and Bulk Rna-seq In Analyzing The H...mentioning

confidence: 61%

“…The primary antibodies and secondary fluorescent antibodies used in this study are listed in Table 1. The primary antibodies have been characterized well in previous studies (Jiang et al., 2022; Jones & Warchol, 2009; Kawai et al., 2021; Morgan et al., 2016; You et al., 2022). Nuclei were labeled with DAPI (1:800 dilution, Sigma‐Aldrich, D9542) for 10 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

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Cross‐species analysis and comparison of the inner ear between chickens and mice

Zhang

Mao

et al. 2023

J of Comparative Neurology

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The inner ear of mammals includes the cochlea and vestibule, which house specialized hair cells that are responsible for hearing and balance, respectively. While cochlear hair cells fail to regenerate following damage, those of the utricle, which is part of the vestibular apparatus, show partial regeneration. In birds, the macula lagena, a unique ear structure in this clade, has the ability to regenerate hair cells similarly to the utricle. Many studies have sought to explain regeneration in terms of evolution and species differences. However, it remains unclear what the cellular and molecular basis is behind the differences in inner ear structures and between avians and mammals. In the present study, we first investigated the anatomical structures of the inner ear of both chickens and rodents. We then performed RNA sequencing (RNA‐Seq) and made cross‐species analyses of the expression of homologous genes obtained from the inner ear tissue from both chickens and mice. Finally, we focused on the lagena, the basilar papilla, and the utricle in chickens and identified differentially expressed genes between tissues and determined the expression patterns of genes involved in inner ear structure formation by single‐cell RNA sequencing and bulk RNA‐Seq. We concluded that the cellular and molecular composition of the lagena is more similar to that of the utricle than the cochlea. Taken together, our study provides a valuable resource for the study of inner ear evolution and development.

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Section: Integration Of Scrna-seq and Bulk Rna-seq In Analyzing The H...mentioning

confidence: 61%

Section: Methodsmentioning

confidence: 99%

Cross‐species analysis and comparison of the inner ear between chickens and mice

Zhang

Mao

et al. 2023

J of Comparative Neurology

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“…FABP5 has been widely reported in autoimmune diseases such as multiple sclerosis, inflammatory neuronal remodeling, and DCs dysregulation ( 25 – 27 ). Similarly, CD47 and UBE2F are involved in aberrant functions of DCs and T cells in various tumors ( 28 – 30 ), indicating their potential relevance to psoriasis development. The random forest algorithm thus demonstrated high accuracy in predicting psoriasis.…”

Section: Resultsmentioning

confidence: 99%

Single-cell sequencing analysis and multiple machine-learning models revealed the cellular crosstalk of dendritic cells and identified FABP5 and KLRB1 as novel biomarkers for psoriasis

Ma,

An,

Hao

et al. 2024

Front. Immunol.

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BackgroundPsoriasis is an immune-mediated disorder influenced by environmental factors on a genetic basis. Despite advancements, challenges persist, including the diminishing efficacy of biologics and small-molecule targeted agents, alongside managing recurrence and psoriasis-related comorbidities. Unraveling the underlying pathogenesis and identifying valuable biomarkers remain pivotal for diagnosing and treating psoriasis.MethodsWe employed a series of bioinformatics (including single-cell sequencing data analysis and machine learning techniques) and statistical methods to integrate and analyze multi-level data. We observed the cellular changes in psoriatic skin tissues, screened the key genes Fatty acid binding protein 5 (FABP5) and The killer cell lectin-like receptor B1 (KLRB1), evaluated the efficacy of six widely prescribed drugs on psoriasis treatment in modulating the dendritic cell-associated pathway, and assessed their overall efficacy. Finally, RT-qPCR, immunohistochemistry, and immunofluorescence assays were used to validate.ResultsThe regulatory influence of dendritic cells (DCs) on T cells through the CD70/CD27 signaling pathway may emerge as a significant facet of the inflammatory response in psoriasis. Notably, FABP5 and KLRB1 exhibited up-regulation and co-localization in psoriatic skin tissues and M5-induced HaCaT cells, serving as potential biomarkers influencing psoriasis development.ConclusionOur study analyzed the impact of DC-T cell crosstalk in psoriasis, elucidated the characterization of two biomarkers, FABP5 and KLRB1, in psoriasis, and highlighted the promise and value of tofacitinib in psoriasis therapy targeting DCs.

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“…Whether TREM2 also plays a role in the excessive pre-synaptic elimi-nation that we showed here or whether, other "eat-me", "don't eat-me", and/or complement regulatory molecules (CD47, SIRPα, CSMD1/2, neuronal pentraxins) [63][64][65][66][67] are involved are yet to be determined and will likely direct future therapeutic targets. It will also be intriguing to determine if C1q at the high levels seen in AD would interfere with the action of several C1q-like molecules expressed in the nervous system that play roles in synapse formation and function.…”

Section: Discussionmentioning

confidence: 99%

C5aR1 signaling promotes region‐ and age‐dependent synaptic pruning in models of Alzheimer's disease

Gomez‐Arboledas,

Fonseca,

Kramar

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONSynaptic loss is a hallmark of Alzheimer's disease (AD) that correlates with cognitive decline in AD patients. Complement‐mediated synaptic pruning has been associated with this excessive loss of synapses in AD. Here, we investigated the effect of C5aR1 inhibition on microglial and astroglial synaptic pruning in two mouse models of AD.METHODSA combination of super‐resolution and confocal and tridimensional image reconstruction was used to assess the effect of genetic ablation or pharmacological inhibition of C5aR1 on the Arctic48 and Tg2576 models of AD.RESULTSGenetic ablation or pharmacological inhibition of C5aR1 partially rescues excessive pre‐synaptic pruning and synaptic loss in an age and region‐dependent fashion in two mouse models of AD, which correlates with improved long‐term potentiation (LTP).DISCUSSIONReduction of excessive synaptic pruning is an additional beneficial outcome of the suppression of C5a‐C5aR1 signaling, further supporting its potential as an effective targeted therapy to treat AD.Highlights C5aR1 ablation restores long‐term potentiation in the Arctic model of AD. C5aR1 ablation rescues region specific excessive pre‐synaptic loss. C5aR1 antagonist, PMX205, rescues VGlut1 loss in the Tg2576 model of AD. C1q tagging is not sufficient to induce VGlut1 microglial ingestion. Astrocytes contribute to excessive pre‐synaptic loss at late stages of the disease.

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Neuronal signal-regulatory protein alpha drives microglial phagocytosis by limiting microglial interaction with CD47 in the retina

Cited by 31 publications

References 100 publications

Cross‐species analysis and comparison of the inner ear between chickens and mice

Cross‐species analysis and comparison of the inner ear between chickens and mice

Single-cell sequencing analysis and multiple machine-learning models revealed the cellular crosstalk of dendritic cells and identified FABP5 and KLRB1 as novel biomarkers for psoriasis

C5aR1 signaling promotes region‐ and age‐dependent synaptic pruning in models of Alzheimer's disease

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