Highly multiplexed imaging mass cytometry identifies similarities between antisynthetase syndrome and dermatomyositis skin lesions

2021 ◽  
Author(s):  
Jay Patel ◽  
Adarsh Ravishankar ◽  
Spandana Maddukuri ◽  
Thomas Vazquez ◽  
Madison Grinnell ◽  
...  
Pathology ◽  
2021 ◽  
Vol 53 ◽  
pp. S36-S37
Author(s):  
Minh Tran ◽  
Andrew Su ◽  
HoJoon Lee ◽  
Richard Cruz ◽  
Lance Pflieger ◽  
...  

Cell Systems ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 531 ◽  
Author(s):  
Daniel Schulz ◽  
Vito Riccardo Tomaso Zanotelli ◽  
Jana Raja Fischer ◽  
Denis Schapiro ◽  
Stefanie Engler ◽  
...  

2021 ◽  
Author(s):  
Febe van Maldegem ◽  
Karishma Valand ◽  
Megan Cole ◽  
Harshil Patel ◽  
Mihaela Angelova ◽  
...  

AbstractMouse models are critical in pre-clinical studies of cancer therapy, allowing dissection of mechanisms through chemical and genetic manipulations that are not feasible in the clinical setting. In studies of the tumour microenvironment (TME), novel highly multiplexed imaging methods can provide a rich source of information. However, the application of such technologies in mouse tissues is still in its infancy. Here we present a workflow for studying the TME using imaging mass cytometry with a panel of 27 antibodies on frozen mouse tissues. We optimised and validated image segmentation strategies and automated the process in a Nextflow-based pipeline (imcyto) that is scalable and portable, allowing for parallelised segmentation of large multi-image datasets. Incorporating user-specific plugins, imcyto can be flexibly tailored to a wide range of segmentation needs. With these methods we interrogated the dramatic remodelling of the TME induced by a KRAS G12C inhibitor in an immune competent mouse orthotopic lung cancer model, showcasing their potential as key discovery tools to enhance understanding of the interplay between tumour, stroma, and immune cells in the spatial context of the tissue.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xu Xiao ◽  
Ying Qiao ◽  
Yudi Jiao ◽  
Na Fu ◽  
Wenxian Yang ◽  
...  

Highly multiplexed imaging technology is a powerful tool to facilitate understanding the composition and interactions of cells in tumor microenvironments at subcellular resolution, which is crucial for both basic research and clinical applications. Imaging mass cytometry (IMC), a multiplex imaging method recently introduced, can measure up to 100 markers simultaneously in one tissue section by using a high-resolution laser with a mass cytometer. However, due to its high resolution and large number of channels, how to process and interpret the image data from IMC remains a key challenge to its further applications. Accurate and reliable single cell segmentation is the first and a critical step to process IMC image data. Unfortunately, existing segmentation pipelines either produce inaccurate cell segmentation results or require manual annotation, which is very time consuming. Here, we developed Dice-XMBD1, a Deep learnIng-based Cell sEgmentation algorithm for tissue multiplexed imaging data. In comparison with other state-of-the-art cell segmentation methods currently used for IMC images, Dice-XMBD generates more accurate single cell masks efficiently on IMC images produced with different nuclear, membrane, and cytoplasm markers. All codes and datasets are available at https://github.com/xmuyulab/Dice-XMBD.


2019 ◽  
Author(s):  
Valeria Ramaglia ◽  
Salma Sheikh-Mohamed ◽  
Karen Legg ◽  
Olga L Rojas ◽  
Stephanie Zandee ◽  
...  

ABSTRACTMultiple Sclerosis (MS) is characterized by demyelinated and inflammatory lesions in the brain and spinal cord. Lesions contain immune cells with variable phenotypes and functions. Here we use imaging mass cytometry (IMC) to enable the simultaneous imaging of 15+ proteins within 11 staged MS lesions. Using this approach, we demonstrated that the majority of demyelinating macrophage-like cells in active lesions were derived from the resident microglial pool. Although CD8+ T cells predominantly infiltrated the lesions, CD4+ T cells were also abundant but localized closer to blood vessels. B cells with a predominant switched memory phenotype were enriched across all lesion stages and were found to preferentially infiltrate the tissue as compared to unswitched B cells which localized to the vasculature. We propose that IMC will enable a comprehensive analysis of single-cell phenotypes, their functional states and cell-cell interactions in relation to lesion morphometry and demyelinating activity in the MS brain.


Cell Systems ◽  
2018 ◽  
Vol 6 (1) ◽  
pp. 25-36.e5 ◽  
Author(s):  
Daniel Schulz ◽  
Vito Riccardo Tomaso Zanotelli ◽  
Jana Raja Fischer ◽  
Denis Schapiro ◽  
Stefanie Engler ◽  
...  

2018 ◽  
Author(s):  
Navi Mehra ◽  
Carsten Schnatwinkel ◽  
Elliott Ergon ◽  
Joseph Krueger ◽  
Karl Calara-Nielsen ◽  
...  

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Valeria Ramaglia ◽  
Salma Sheikh-Mohamed ◽  
Karen Legg ◽  
Calvin Park ◽  
Olga L Rojas ◽  
...  

Multiple sclerosis (MS) is characterized by demyelinated and inflammatory lesions in the brain and spinal cord that are highly variable in terms of cellular content. Here, we used imaging mass cytometry (IMC) to enable the simultaneous imaging of 15+ proteins within staged MS lesions. To test the potential for IMC to discriminate between different types of lesions, we selected a case with severe rebound MS disease activity after natalizumab cessation. With post-acquisition analysis pipelines we were able to: (1) Discriminate demyelinating macrophages from the resident microglial pool; (2) Determine which types of lymphocytes reside closest to blood vessels; (3) Identify multiple subsets of T and B cells, and (4) Ascertain dynamics of T cell phenotypes vis-à-vis lesion type and location. We propose that IMC will enable a comprehensive analysis of single-cell phenotypes, their functional states and cell-cell interactions in relation to lesion morphometry and demyelinating activity in MS patients.


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