Spatial proteomics in three-dimensional intact specimens

Bhatia, Harsharan S.; Brunner, Andreas-David; Öztürk, Furkan; Kapoor, Saketh; Rong, Zhouyi; Mai, Hongcheng; Thielert, Marvin; Ali, Mayar; Al-Maskari, Rami; Paetzold, Johannes C.; Kofler, Florian; Todorov, Mihail Ivilinov; Molbay, Muge; Kolabas, Zeynep Ilgin; Negwer, Moritz; Hoeher, Luciano; Steinke, Hanno; Dima, Alina; Gupta, Basavdatta; Kaltenecker, Doris; Çalışkan, Özüm Şehnaz; Brandt, D.; Krahmer, Natalie; Müller, Stephan; Lichtenthaler, Stefan F.; Hellal, Farida; Bechmann, Ingo; Menze, Bjoern H.; Theis, Fabian J.; Mann, Matthias; Ertürk, Ali

doi:10.1016/j.cell.2022.11.021

Cited by 35 publications

(31 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A comparison of datasets from the skull marrow, meninges, and brain samples identified five common differentially expressed proteins related to antigen presentation and recognition, including IGHV1-3, HLA-B, APCS, ISG15, and MX1, whereas MX1 is known to have an antiviral function 74 . To further pinpoint the consequences of spike proteinspecific effects in the brain tissue beyond the acute inflammatory response, we performed targeted proteomics on laser capture micro-dissected tissues 75 by analyzing the spike positive vs. spike negative brain regions (Fig. 3I).…”

Section: Proteomics Profiling Of Covid-19 Patient Skull Marrow Mening...mentioning

confidence: 99%

SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19

Rong

Mai

Kapoor

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has been associated mainly with a range of neurological symptoms, including brain fog and brain tissue loss, raising concerns about the virus's acute and potential chronic impact on the central nervous system. In this study, we utilized mouse models and human post-mortem tissues to investigate the presence and distribution of the SARS-CoV-2 spike protein in the skull-meninges-brain axis. Our results revealed the accumulation of the spike protein in the skull marrow, brain meninges, and brain parenchyma. The injection of the spike protein alone caused cell death in the brain, highlighting a direct effect on brain tissue. Furthermore, we observed the presence of spike protein in the skull of deceased long after their COVID-19 infection, suggesting that the spike's persistence may contribute to long-term neurological symptoms. The spike protein was associated with neutrophil-related pathways and dysregulation of the proteins involved in the PI3K-AKT as well as complement and coagulation pathway. Overall, our findings suggest that SARS-CoV-2 spike protein trafficking from CNS borders into the brain parenchyma and identified differentially regulated pathways may present insights into mechanisms underlying immediate and long-term consequences of SARS-CoV-2 and present diagnostic and therapeutic opportunities.

show abstract

Section: Proteomics Profiling Of Covid-19 Patient Skull Marrow Mening...mentioning

confidence: 99%

SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19

Rong

Mai

Kapoor

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Applying these techniques to microglia derived from AD patient stem cells or isolated from AD brain tissue will further validate subclusters at a protein level. The use of spatial proteomics at the single‐cell level has recently been applied to AD post‐mortem tissue and will enable the landscape of microglial cluster heterogeneity to be mapped within the brain (Bhatia et al, 2022; Shahidehpour et al, 2023; Vijayaragavan et al, 2022). Quantitative multiplex immunohistochemistry with visual colorimetric staining to enhance regional protein localization (QUIVER) generates a 10‐channel pseudo‐fluorescent image, which has been applied to AD tissue, and identified five microglia/macrophage molecular phenotypes in relation to AD pathology (Shahidehpour et al, 2023).…”

Section: Defining Microglial States Using Single‐cell and Single‐nucl...mentioning

confidence: 99%

Innovations advancing our understanding of microglia in Alzheimer's disease: From in vitro to in vivo models

Maksour

Ooi

2023

Journal of Neurochemistry

View full text Add to dashboard Cite

Microglia have been implicated in Alzheimer's disease (AD) pathogenesis through the identification of risk factor genes that are specifically or predominantly expressed in this cell type. Additional evidence suggests that microglia undergo dramatic morphological and phenotypic state changes during AD progression, as observed in human post-mortem tissue and animal model research. Although valuable, these studies are often hampered by either representing one time point in human tissue (end point) or because of the lack of conservation between species of microglial transcriptomes, proteomes and cell states. Thus, the development and application of novel human model systems have been beneficial in the study of microglia in neurodegeneration.Recent innovations include the use of human pluripotent stem cell (hPSC)-derived microglia in 2D or 3D culture systems, the transdifferentiation of microglia from patient monocytes and the xenotransplantation of hPSC-derived microglia into mouse brains. This review summarizes the recent innovations that have advanced our understanding of microglia in AD, through the use of single-cell RNA sequencing, hPSC-derived microglia culture within brain organoids and xenotransplantation into mouse brain.Through outlining the strengths and limitations of these approaches, we provide recommendations that will aid future endeavours in advancing our understanding of the complex role of microglia in AD onset and progression.

show abstract

“…Most spatial proteome analysis are limited to the number of analysed proteins [27–29]. Bhatia et al [30 ▪▪ ] presented a spatial proteomics protocol termed DISCO-MS, in which tissue clearing was combined with mass spectrometry. In this study, up to 8000 proteins were detected in cleared mouse brains.…”

Section: Tissue Clearing Protocolsmentioning

confidence: 99%

The use of tissue clearing to study renal transport mechanisms and kidney remodelling

Saritas

2023

Current Opinion in Nephrology &Amp; Hypertension

View full text Add to dashboard Cite

Purpose of reviewTissue clearing enables examination of biological structures at subcellular resolution in three dimensions. It uncovered the spatial and temporal plasticity of multicellular kidney structures that occur during homeostatic stress. This article will review the recent development in tissue clearing protocols and how it facilitated the study of renal transport mechanisms and remodelling of the kidney.Recent findingsTissue clearing methods have evolved from primarily labelling proteins in thin tissue or individual organs to visualizing both RNA and protein simultaneously in whole animals or human organs. The use of small antibody fragments and innovative imaging techniques improved immunolabelling and resolution. These advances opened up new avenues for studying organ crosstalk and diseases that affect multiple parts of the organism. Accumulating evidence suggests that tubule remodelling can occur rapidly in response to homeostatic stress or injury, allowing for adjustments in the quantitative expression of renal transporters. Tissue clearing helped to better understand the development of tubule cystogenesis, renal hypertension and salt wasting syndromes, and revealed potential progenitor cells in the kidney.SummaryThe continued evolution and improvement of tissue clearing methods can help to gain deep biological insights into the structure and function of the kidney, which will have clinical implications.

show abstract

Spatial proteomics in three-dimensional intact specimens

Cited by 35 publications

References 80 publications

SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19

SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19

Innovations advancing our understanding of microglia in Alzheimer's disease: From in vitro to in vivo models

The use of tissue clearing to study renal transport mechanisms and kidney remodelling

Contact Info

Product

Resources

About