4.7 Review

Profiling Cell Signaling Networks at Single-cell Resolution

期刊

MOLECULAR & CELLULAR PROTEOMICS
卷 19, 期 5, 页码 744-756

出版社

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/mcp.R119.001790

关键词

Signaling circuits; phosphoproteome; systems biology; assay development; pathway analysis; single-cell analysis

资金

  1. SNSF R'Equip grant
  2. SNSF Assistant Professorship grant [PP00P3-144874]
  3. European Research Council (ERC) under the European Union's Seventh Framework Program (FP/2007-2013)/ERC Grant [336921]
  4. NIH [UC4 DK108132]
  5. Swiss National Science Foundation (SNF) [PP00P3_144874] Funding Source: Swiss National Science Foundation (SNF)

向作者/读者索取更多资源

Signaling networks process intra- and extracellular information to modulate the functions of a cell. Deregulation of signaling networks results in abnormal cellular physiological states and often drives diseases. Network responses to a stimulus or a drug treatment can be highly heterogeneous across cells in a tissue because of many sources of cellular genetic and non-genetic variance. Signaling network heterogeneity is the key to many biological processes, such as cell differentiation and drug resistance. Only recently, the emergence of multiplexed single-cell measurement technologies has made it possible to evaluate this heterogeneity. In this review, we categorize currently established single-cell signaling network profiling approaches by their methodology, coverage, and application, and we discuss the advantages and limitations of each type of technology. We also describe the available computational tools for network characterization using single-cell data and discuss potential confounding factors that need to be considered in single-cell signaling network analyses.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Allergy

Cutaneous and systemic hyperinflammation drives maculopapular drug exanthema in severely ill COVID-19 patients

Yasutaka Mitamura, Daniel Schulz, Saskia Oro, Nick Li, Isabel Kolm, Claudia Lang, Reihane Ziadlou, Ge Tan, Bernd Bodenmiller, Peter Steiger, Angelo Marzano, Nicolas de Prost, Olivier Caudin, Mitchell Levesque, Corinne Stoffel, Peter Schmid-Grendelmeier, Emanual Maverakis, Cezmi A. Akdis, Marie-Charlotte Bruggen

Summary: This study found that COVID-MDR in COVID-19 patients exhibited a more prominent and phenotypically shifted cellular infiltrate, along with a more robust cytotoxic response in skin, although SARS-CoV-2 was not detected in skin samples at the time of MDR diagnosis. Serum proteomic profiling of COVID-MDR patients revealed upregulation of various inflammatory mediators, indicating a massive systemic cytokine storm.

ALLERGY (2022)

Article Multidisciplinary Sciences

Mass cytometric and transcriptomic profiling of epithelial-mesenchymal transitions in human mammary cell lines

Johanna Wagner, Markus Masek, Andrea Jacobs, Charlotte Soneson, Sujana Sivapatham, Nicolas Damond, Natalie de Souza, Mark D. Robinson, Bernd Bodenmiller

Summary: In this study, the EMT transition phenotypes in four non-cancerous human mammary epithelial cell lines were comprehensively profiled and compared to breast cancer cell lines. The results revealed a spectrum of EMT transition phenotypes in each cell line. These findings contribute to a better understanding of the complexity of EMT and provide valuable insights for the design of EMT time course experiments.

SCIENTIFIC DATA (2022)

Article Allergy

T-cell recovery and evidence of persistent immune activation 12 months after severe COVID-19

Patrick Taeschler, Sarah Adamo, Yun Deng, Carlo Cervia, Yves Zurbuchen, Stephane Chevrier, Miro E. Raeber, Sara Hasler, Esther Bachli, Alain Rudiger, Melina Stussi-Helbling, Lars C. Huber, Bernd Bodenmiller, Onur Boyman, Jakob Nilsson

Summary: This study suggests that most patients recover T-cell numbers and function after COVID-19. However, there is evidence of persistent T-cell activation up to 12 months after infection and a subgroup of severe COVID-19 patients exhibit a dysregulated immune response during acute infection.

ALLERGY (2022)

Article Genetics & Heredity

Breast tumor microenvironment structures are associated with genomic features and clinical outcome

Esther Danenberg, Helen Bardwell, Vito R. T. Zanotelli, Elena Provenzano, Suet-Feung Chin, Oscar M. Rueda, Andrew Green, Emad Rakha, Samuel Aparicio, Ian O. Ellis, Bernd Bodenmiller, Carlos Caldas, H. Raza Ali

Summary: Imaging mass cytometry profiling of 693 breast tumors revealed 10 recurrent tumor microenvironment spatial structures, associated with genomic profiles and outcomes. These multicellular structures within the TME, varying in vascular content, stromal activation, and leukocyte composition, could improve patient stratification and link spatial organization to local TME function.

NATURE GENETICS (2022)

Article Immunology

Multiplexed imaging mass cytometry of the chemokine milieus in melanoma characterizes features of the response to immunotherapy

Tobias Hoch, Daniel Schulz, Nils Eling, Julia Martinez Gomez, Mitchell P. Levesque, Bernd Bodenmiller

Summary: Intratumoral immune cells play a crucial role in tumor control and antitumor responses during immunotherapy. This study analyzed the chemokine expression and immune infiltration in melanoma using multiplexed mass cytometry-based imaging, and found that tumors lacking immune infiltration had low levels of chemokines, antigen presentation, and markers of inflammation, while infiltrated tumors expressed multiple chemokines.

SCIENCE IMMUNOLOGY (2022)

Article Neurosciences

A shared disease-associated oligodendrocyte signature among multiple CNS pathologies

Mor Kenigsbuch, Pierre Bost, Shahar Halevi, Yuzhou Chang, Shuo Chen, Qin Ma, Renana Hajbi, Benno Schwikowski, Bernd Bodenmiller, Hongjun Fu, Michal Schwartz, Ido Amit

Summary: This study identifies a shared signature of oligodendrocytes in central nervous system pathologies. The researchers discovered a specific oligodendrocyte state, termed disease-associated oligodendrocytes (DOLs), that increased with brain pathology. DOLs were found in various neurodegenerative and inflammatory conditions, indicating a common response to severe pathological conditions.

NATURE NEUROSCIENCE (2022)

Article Oncology

Vaccination with Designed Neopeptides Induces Intratumoral, Cross-reactive CD4+T-cell Responses in Glioblastoma

Jian Wang, Tobias Weiss, Marian C. Neidert, Nora C. Toussaint, Reza Naghavian, Carla Selles Moreno, Magdalena Foege, Paula Tomas Ojer, Gioele Medici, Ivan Jelcic, Daniel Schulz, Elisabeth Rushing, Susanne Dettwiler, Barbara Schrors, Joo Heon Shin, Ron McKay, Catherine J. Wu, Andreas Lutterotti, Mireia Sospedra, Holger Moch, Erich F. Greiner, Bernd Bodenmiller, Luca Regli, Michael Weller, Patrick Roth, Roland Martin

Summary: The study developed a strategy to design neopeptides with enhanced immunogenicity through single amino acid mutations. Vaccination with these peptides resulted in immune responses from CD8+ T cells and CD4+ T cells upon tumor recurrence.

CLINICAL CANCER RESEARCH (2022)

Article Multidisciplinary Sciences

Single-cell genomic variation induced by mutational processes in cancer

Tyler Funnell, Ciara H. O'Flanagan, Marc J. Williams, Andrew McPherson, Steven McKinney, Farhia Kabeer, Hakwoo Lee, Sohrab Salehi, Ignacio Vazquez-Garcia, Hongyu Shi, Emily Leventhal, Tehmina Masud, Peter Eirew, Damian Yap, Allen W. Zhang, Jamie L. P. Lim, Beixi Wang, Jazmine Brimhall, Justina Biele, Jerome Ting, Vinci Au, Michael Van Vliet, Yi Fei Liu, Sean Beatty, Daniel Lai, Jenifer Pham, Diljot Grewal, Douglas Abrams, Eliyahu Havasov, Samantha Leung, Viktoria Bojilova, Richard A. Moore, Nicole Rusk, Florian Uhlitz, Nicholas Ceglia, Adam C. Weiner, Elena Zaikova, J. Maxwell Douglas, Dmitriy Zamarin, Britta Weigelt, Sarah H. Kim, Arnaud Da Cruz Paula, Jorge S. Reis-Filho, Spencer D. Martin, Yangguang Li, Hong Xu, Teresa Ruiz de Algara, So Ra Lee, Viviana Cerda Llanos, David G. Huntsman, Jessica N. McAlpine, Sohrab P. Shah, Samuel Aparicio

Summary: This study reveals the contribution of cell-to-cell structural variation to the phenotypic and evolutionary diversity in human breast cancer and ovarian cancer, and provides insights into the genomic and mutational states of individual cancer cells.

NATURE (2022)

Article Biochemical Research Methods

Optimizing multiplexed imaging experimental design through tissue spatial segregation estimation

Pierre Bost, Daniel Schulz, Stefanie Engler, Clive Wasserfall, Bernd Bodenmiller

Summary: Recent advances in multiplexed imaging methods have allowed for simultaneous detection of multiple proteins and RNAs, providing a deeper understanding of the spatial characteristics of healthy and diseased tissues. However, optimal design parameters for multiplex imaging studies, particularly in capturing all cell phenotype clusters, are currently lacking. In this study, a statistical framework using a spatial transcriptomic atlas was developed to determine the number and area of fields of view needed to accurately identify all cell phenotypes in a tissue. This strategy, applied to imaging mass cytometry data, identified a measure of tissue spatial segregation that enables optimal experimental design, thus improving the design of multiplexed imaging studies.

NATURE METHODS (2023)

Correction Neurosciences

A shared disease-associated oligodendrocyte signature among multiple CNS pathologies (vol 25, pg 876, 2022)

Mor Kenigsbuch, Pierre Bost, Shahar Halevi, Yuzhou Chang, Shuo Chen, Qin Ma, Renana Hajbi, Benno Schwikowski, Bernd Bodenmiller, Hongjun Fu, Michal Schwartz, Ido Amit

NATURE NEUROSCIENCE (2023)

Article Multidisciplinary Sciences

A comprehensive single-cell map of T cell exhaustion-associated immune environments in human breast cancer

Sandra Tietscher, Johanna Wagner, Tobias Anzeneder, Claus Langwieder, Martin Rees, Bettina Sobottka, Natalie de Souza, Bernd Bodenmiller

Summary: Immune checkpoint therapy in breast cancer is limited to triple negative patients and shows rare long-term clinical benefit. This study explores the immune environments of human breast tumors with or without exhausted T cells, focusing on luminal subtypes. The presence of a PD-1(high) exhaustion-like T cell phenotype is associated with an inflammatory immune environment, increased myeloid cell activation, elevated immunomodulatory and cytokine signaling, accumulation of natural killer T cells, and altered spatial organization. PD-1 and CXCL13 expression on T cells, and MHC-I expression on tumor cells are distinguishing features between the immune environments.

NATURE COMMUNICATIONS (2023)

Article Biology

Clonal transcriptomics identifies mechanisms of chemoresistance and empowers rational design of combination therapies

Sophia A. Wild, Ian G. Cannell, Ashley Nicholls, Katarzyna Kania, Dario Bressan, Gregory J. Hannon, Kirsty Sawicka

Summary: This study utilizes clonal transcriptomics with WILD-seq to analyze mouse models of TNBC and identifies NRF2 as a major mechanism of taxane resistance. It also discovers the collateral sensitivity of tumor models to asparagine deprivation therapy using L-asparaginase after docetaxel treatment.
Article Oncology

ROS Induction Targets Persister Cancer Cells with Low Metabolic Activity in NRAS-Mutated Melanoma

Ossia M. Eichhoff, Corinne I. Stoffel, Jan Kasler, Luzia Briker, Patrick Turko, Gergely Karsai, Nina Zila, Verena Paulitschke, Phil F. Cheng, Alexander Leitner, Andrea Bileck, Nicola Zamboni, Anja Irmisch, Zsolt Balazs, Aizhan Tastanova, Susana Pascoal, Pal Johansen, Rebekka Wegmann, Julien Mena, Alaa Othman, Vasanthi S. Viswanathan, Judith Wenzina, Andrea Aloia, Annalisa Saltari, Andreas Dzung, Michael Krauthammer, Stuart L. Schreiber, Thorsten Hornemann, Martin Distel, Berend Snijder, Reinhard Dummer, Mitchell P. Levesque

Summary: The clinical management of NRAS-mutated melanomas is challenging due to resistance that arises through genetic, transcriptional, and metabolic adaptation. However, the adoption of a mesenchymal phenotype with a quiescent metabolic program in NRAS-mutated melanoma cells confers sensitivity to reactive oxygen species (ROS) induction, which can be inhibited by ROS inducers in combination with MAPK pathway inhibitors. The findings suggest that targeting both metabolic reprogramming and MAPK signaling could improve patient treatment in melanoma and other cancers.

CANCER RESEARCH (2023)

Article Cell Biology

Multiplex imaging of breast cancer lymph node metastases identifies prognostic single-cell populations independent of clinical classifiers

Jana Raja Fischer, Hartland Warren Jackson, Natalie de Souza, Zsuzsanna Varga, Peter Schraml, Holger Moch, Bernd Bodenmiller

Summary: Although breast cancer mortality is caused by metastasis, clinical decisions are not based on the phenotype of disseminated cells. This study compares single-cell phenotypes of primary breast tumors and matched lymph node metastases using multiplex imaging mass cytometry. The researchers observe extensive phenotypic variability between primary and metastatic sites, and identify single-cell phenotypes and spatial organizations of disseminated tumor cells associated with patient survival. They also find that p53 and GATA3 in lymph node metastases provide prognostic information beyond clinical classifiers.

CELL REPORTS MEDICINE (2023)

Article Oncology

Three-dimensional imaging mass cytometry for highly multiplexed molecular and cellular mapping of tissues and the tumor microenvironment

Laura Kuett, Raul Catena, Alaz Ozcan, Alex Pluss, Peter Schraml, Holger Moch, Natalie de Souza, Bernd Bodenmiller

Summary: The article introduces a new imaging mass cytometry technology that allows for multiplexed tissue analysis in three dimensions. The study shows that this technology can reveal the complexity of cells and microenvironments, as well as phenomena occurring in three-dimensional space, such as tumor cell invasion.

NATURE CANCER (2022)

暂无数据