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Article: Multiplex Tissue Imaging: Spatial Revelations in the Tumor Microenvironment.

van Dam, Stephanie / Baars, Matthijs J D / Vercoulen, Yvonne

2022 Volume 14, Issue 13

Abstract: The tumor microenvironment is a complex ecosystem containing various cell types, such as immune cells, fibroblasts, and endothelial cells, which interact with the tumor cells. In recent decades, the cancer research field has gained insight into the ... ...

Abstract	The tumor microenvironment is a complex ecosystem containing various cell types, such as immune cells, fibroblasts, and endothelial cells, which interact with the tumor cells. In recent decades, the cancer research field has gained insight into the cellular subtypes that are involved in tumor microenvironment heterogeneity. Moreover, it has become evident that cellular interactions in the tumor microenvironment can either promote or inhibit tumor development, progression, and drug resistance, depending on the context. Multiplex spatial analysis methods have recently been developed; these have offered insight into how cellular crosstalk dynamics and heterogeneity affect cancer prognoses and responses to treatment. Multiplex (imaging) technologies and computational analysis methods allow for the spatial visualization and quantification of cell-cell interactions and properties. These technological advances allow for the discovery of cellular interactions within the tumor microenvironment and provide detailed single-cell information on properties that define cellular behavior. Such analyses give insights into the prognosis and mechanisms of therapy resistance, which is still an urgent problem in the treatment of multiple types of cancer. Here, we provide an overview of multiplex imaging technologies and concepts of downstream analysis methods to investigate cell-cell interactions, how these studies have advanced cancer research, and their potential clinical implications.
Language	English
Publishing date	2022-06-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14133170
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Dietary cystine restriction increases the proliferative capacity of the small intestine of mice.

de Jong, Judith C W / van Rooijen, Kristel S / Stigter, Edwin C A / Gülersönmez, M Can / de Zoete, Marcel R / Top, Janetta / Baars, Matthijs J D / Vercoulen, Yvonne / Kuipers, Folkert / van Mil, Saskia W C / Ijssennagger, Noortje

PloS one

2024 Volume 19, Issue 1, Page(s) e0290493

Abstract: Currently, over 88 million people are estimated to have adopted a vegan or vegetarian diet. Cysteine is a semi-essential amino acid, which availability is largely dependent on dietary intake of meat, eggs and whole grains. Vegan/vegetarian diets are ... ...

Abstract	Currently, over 88 million people are estimated to have adopted a vegan or vegetarian diet. Cysteine is a semi-essential amino acid, which availability is largely dependent on dietary intake of meat, eggs and whole grains. Vegan/vegetarian diets are therefore inherently low in cysteine. Sufficient uptake of cysteine is crucial, as it serves as substrate for protein synthesis and can be converted to taurine and glutathione. We found earlier that intermolecular cystine bridges are essential for the barrier function of the intestinal mucus layer. Therefore, we now investigate the effect of low dietary cystine on the intestine. Mice (8/group) received a high fat diet with a normal or low cystine concentration for 2 weeks. We observed no changes in plasma methionine, cysteine, taurine or glutathione levels or bile acid conjugation after 2 weeks of low cystine feeding. In the colon, dietary cystine restriction results in an increase in goblet cell numbers, and a borderline significant increase mucus layer thickness. Gut microbiome composition and expression of stem cell markers did not change on the low cystine diet. Remarkably, stem cell markers, as well as the proliferation marker Ki67, were increased upon cystine restriction in the small intestine. In line with this, gene set enrichment analysis indicated enrichment of Wnt signaling in the small intestine of mice on the low cystine diet, indicative of increased epithelial proliferation. In conclusion, 2 weeks of cystine restriction did not result in apparent systemic effects, but the low cystine diet increased the proliferative capacity specifically of the small intestine and induced the number of goblet cells in the colon.
MeSH term(s)	Humans ; Animals ; Mice ; Cystine ; Cysteine ; Intestine, Small ; Glutathione ; Taurine
Chemical Substances	Cystine (48TCX9A1VT) ; Cysteine (K848JZ4886) ; Glutathione (GAN16C9B8O) ; Taurine (1EQV5MLY3D)
Language	English
Publishing date	2024-01-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0290493
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: MATISSE: An analysis protocol for combining imaging mass cytometry with fluorescence microscopy to generate single-cell data.

Krijgsman, Daniëlle / Sinha, Neeraj / Baars, Matthijs J D / van Dam, Stephanie / Amini, Mojtaba / Vercoulen, Yvonne

STAR protocols

2021 Volume 3, Issue 1, Page(s) 101034

Abstract: Exploring tissue heterogeneity on a single-cell level by imaging mass cytometry (IMC) remains challenging because of its limiting resolution. We previously demonstrated that combining higher resolution fluorescence with IMC data in the analysis pipeline ... ...

Abstract	Exploring tissue heterogeneity on a single-cell level by imaging mass cytometry (IMC) remains challenging because of its limiting resolution. We previously demonstrated that combining higher resolution fluorescence with IMC data in the analysis pipeline resulted in high-quality single-cell segmentation. Here, we provide a step-by-step workflow of this MATISSE pipeline, including instructions regarding the staining procedure, and the analysis route to generate single-cell data. For complete details on the use and execution of this protocol, please refer to Baars et al., 2021.
MeSH term(s)	Image Cytometry ; Microscopy, Fluorescence ; Staining and Labeling ; Workflow
Language	English
Publishing date	2021-12-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2021.101034
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Active Tonic mTORC1 Signals Shape Baseline Translation in Naive T Cells.

Myers, Darienne R / Norlin, Emilia / Vercoulen, Yvonne / Roose, Jeroen P

Cell reports

2019 Volume 27, Issue 6, Page(s) 1858–1874.e6

Abstract: ... Naive ... ...

Abstract	Naive CD4
MeSH term(s)	Animals ; Autoimmunity ; Cell Differentiation ; Cell Line ; Chickens ; Guanine Nucleotide Exchange Factors/metabolism ; Humans ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice, Inbred C57BL ; Mice, Transgenic ; Protein Biosynthesis ; Signal Transduction ; T-Lymphocytes/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Th2 Cells/cytology
Chemical Substances	Guanine Nucleotide Exchange Factors ; Rasgrp1 protein, mouse ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1)
Language	English
Publishing date	2019-05-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2019.04.037
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Article ; Online: Stromal localization of inactive CD8

Küçükköse, Emre / Baars, Matthijs J D / Amini, Mojtaba / Schraa, Suzanna J / Floor, Evelien / Bol, Guus M / Borel Rinkes, Inne H M / Roodhart, Jeanine M L / Koopman, Miriam / Laoukili, Jamila / Kranenburg, Onno / Vercoulen, Yvonne

British journal of cancer

2023 Volume 130, Issue 2, Page(s) 213–223

Abstract: Background: The determinants of metastasis in mismatch repair deficiency with high levels of microsatellite instability (MSI-H) in colorectal cancer (CRC) are poorly understood. Here, we hypothesized that distinct immune and stromal microenvironments in ...

Abstract	Background: The determinants of metastasis in mismatch repair deficiency with high levels of microsatellite instability (MSI-H) in colorectal cancer (CRC) are poorly understood. Here, we hypothesized that distinct immune and stromal microenvironments in primary tumors may discriminate between non-metastatic MSI-H CRC and metastatic MSI-H CRC. Methods: We profiled 46,727 single cells using high-plex imaging mass cytometry and analyzed both differential cell type abundance, and spatial distribution of fibroblasts and immune cells in primary CRC tumors with or without metastatic capacity. We validated our findings in a second independent cohort using immunohistochemistry. Results: High-plex imaging mass cytometry and hierarchical clustering based on microenvironmental markers separated primary MSI-H CRC tumors with and without metastatic capacity. Primary tumors with metastatic capacity displayed a high stromal content and low influx of CD8 Conclusion: We conclude that localization of phenotypically distinct CD8
MeSH term(s)	Humans ; CD8-Positive T-Lymphocytes ; DNA Mismatch Repair ; Prognosis ; Colonic Neoplasms ; Colorectal Neoplasms/pathology ; Microsatellite Instability ; Rectal Neoplasms ; Tumor Microenvironment
Language	English
Publishing date	2023-12-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-023-02500-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: MATISSE

Daniëlle Krijgsman / Neeraj Sinha / Matthijs J.D. Baars / Stephanie van Dam / Mojtaba Amini / Yvonne Vercoulen

STAR Protocols, Vol 3, Iss 1, Pp 101034- (2022)

An analysis protocol for combining imaging mass cytometry with fluorescence microscopy to generate single-cell data

2022

Abstract: Summary: Exploring tissue heterogeneity on a single-cell level by imaging mass cytometry (IMC) remains challenging because of its limiting resolution. We previously demonstrated that combining higher resolution fluorescence with IMC data in the analysis ... ...

Abstract	Summary: Exploring tissue heterogeneity on a single-cell level by imaging mass cytometry (IMC) remains challenging because of its limiting resolution. We previously demonstrated that combining higher resolution fluorescence with IMC data in the analysis pipeline resulted in high-quality single-cell segmentation. Here, we provide a step-by-step workflow of this MATISSE pipeline, including instructions regarding the staining procedure, and the analysis route to generate single-cell data.For complete details on the use and execution of this protocol, please refer to Baars et al., 2021.
Keywords	Bioinformatics ; Cell Biology ; Single Cell ; Flow Cytometry/Mass Cytometry ; Microscopy ; Antibody ; Science (General) ; Q1-390
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Dietary cystine restriction increases the proliferative capacity of the small intestine of mice.

Judith C W de Jong / Kristel S van Rooijen / Edwin C A Stigter / M Can Gülersönmez / Marcel R de Zoete / Janetta Top / Matthijs J D Baars / Yvonne Vercoulen / Folkert Kuipers / Saskia W C van Mil / Noortje Ijssennagger

PLoS ONE, Vol 19, Iss 1, p e

2024 Volume 0290493

Abstract	Currently, over 88 million people are estimated to have adopted a vegan or vegetarian diet. Cysteine is a semi-essential amino acid, which availability is largely dependent on dietary intake of meat, eggs and whole grains. Vegan/vegetarian diets are therefore inherently low in cysteine. Sufficient uptake of cysteine is crucial, as it serves as substrate for protein synthesis and can be converted to taurine and glutathione. We found earlier that intermolecular cystine bridges are essential for the barrier function of the intestinal mucus layer. Therefore, we now investigate the effect of low dietary cystine on the intestine. Mice (8/group) received a high fat diet with a normal or low cystine concentration for 2 weeks. We observed no changes in plasma methionine, cysteine, taurine or glutathione levels or bile acid conjugation after 2 weeks of low cystine feeding. In the colon, dietary cystine restriction results in an increase in goblet cell numbers, and a borderline significant increase mucus layer thickness. Gut microbiome composition and expression of stem cell markers did not change on the low cystine diet. Remarkably, stem cell markers, as well as the proliferation marker Ki67, were increased upon cystine restriction in the small intestine. In line with this, gene set enrichment analysis indicated enrichment of Wnt signaling in the small intestine of mice on the low cystine diet, indicative of increased epithelial proliferation. In conclusion, 2 weeks of cystine restriction did not result in apparent systemic effects, but the low cystine diet increased the proliferative capacity specifically of the small intestine and induced the number of goblet cells in the colon.
Keywords	Medicine ; R ; Science ; Q
Subject code	500
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Highly multiplexed spatial analysis identifies tissue-resident memory T cells as drivers of ulcerative and immune checkpoint inhibitor colitis.

van Eijs, Mick J M / Ter Linde, José J M / Baars, Matthijs J D / Amini, Mojtaba / Laclé, Miangela M / Brand, Eelco C / Delemarre, Eveline M / Drylewicz, Julia / Nierkens, Stefan / Verheijden, Rik J / Oldenburg, Bas / Vercoulen, Yvonne / Suijkerbuijk, Karijn P M / van Wijk, Femke

iScience

2023 Volume 26, Issue 10, Page(s) 107891

Abstract: Colitis is a prevalent adverse event associated with immune checkpoint inhibitor (ICI) therapy with similarities to inflammatory bowel disease. Incomplete mechanistic understanding of ICI colitis curtails evidence-based treatment. Given the often- ... ...

Abstract	Colitis is a prevalent adverse event associated with immune checkpoint inhibitor (ICI) therapy with similarities to inflammatory bowel disease. Incomplete mechanistic understanding of ICI colitis curtails evidence-based treatment. Given the often-overlooked connection between tissue architecture and mucosal immune cell function, we here applied imaging mass cytometry (IMC) to gain spatial proteomic insight in ICI colitis in comparison to ulcerative colitis (UC). Using a cell segmentation pipeline that simultaneously utilizes high-resolution nuclear imaging and high-multiplexity IMC, we show that intra-epithelial CD8
Language	English
Publishing date	2023-09-11
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.107891
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Active Tonic mTORC1 Signals Shape Baseline Translation in Naive T Cells

Darienne R. Myers / Emilia Norlin / Yvonne Vercoulen / Jeroen P. Roose

Cell Reports, Vol 27, Iss 6, Pp 1858-1874.e

2019 Volume 6

Abstract: Summary: Naive CD4+ T cells are an example of dynamic cell homeostasis: T cells need to avoid autoreactivity while constantly seeing self-peptides, yet they must be primed to react to foreign antigens during infection. The instructive signals that ... ...

Abstract	Summary: Naive CD4+ T cells are an example of dynamic cell homeostasis: T cells need to avoid autoreactivity while constantly seeing self-peptides, yet they must be primed to react to foreign antigens during infection. The instructive signals that balance this primed yet quiescent state are unknown. Interactions with self-peptides result in membrane-proximal, tonic signals in resting T cells. Here we reveal selective and robust tonic mTORC1 signals in CD4+ T cells that influence T cell fate decisions. We find that the Ras exchange factor Rasgrp1 is necessary to generate tonic mTORC1 signals. Genome-wide ribosome profiling of resting, primary CD4+ T cells uncovers a baseline translational landscape rich in mTOR targets linked to mitochondria, oxidative phosphorylation, and splicing. Aberrantly increased tonic mTORC1 signals from a Rasgrp1Anaef allele result in immunopathology with spontaneous appearance of T peripheral helper cells, follicular helper T cells, and anti-nuclear antibodies that are preceded by subtle alterations in the translational landscape. : Myers et al. evaluate a mouse model of autoimmunity, Rasgrp1Anaef. They find that T cells with the Rasgrp1Anaef allele exhibit altered signaling from Rasgrp1 to the mTORC1 pathway in the basal state. They show that increased basal Rasgrp1Anaef-mTORC1 signals lead to an altered translational landscape in T cells and immunopathology. Keywords: naive T cell, tonic signaling, mTOR, Rasgrp1, Anaef, CD44, CD5, mRNA translation, ribosome profiling, autoimmunity
Keywords	Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2019-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Publisher Correction to: MATISSE: a method for improved single cell segmentation in imaging mass cytometry.

Baars, Matthijs J D / Sinha, Neeraj / Amini, Mojtaba / Pieterman-Bos, Annelies / van Dam, Stephanie / Ganpat, Maroussia M P / Laclé, Miangela M / Oldenburg, Bas / Vercoulen, Yvonne

BMC biology

2021 Volume 19, Issue 1, Page(s) 125

Language	English
Publishing date	2021-06-18
Publishing country	England
Document type	Published Erratum
ISSN	1741-7007
ISSN (online)	1741-7007
DOI	10.1186/s12915-021-01065-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

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