CellCall: integrating paired ligand–receptor and transcription factor activities for cell–cell communication

Zhang, Yang; Liu, Tianyuan; Hu, Xuesong; Wang, Mei; Wang, Jing; Zou, Bohao; Tan, Puwen; Cui, Tianyu; Dou, Yiying; Lin, Ning; Huang, Yan; S, Rao; Wang, Dong; Zhao, Xiaoyang

doi:10.1093/nar/gkab638

Cited by 151 publications

(104 citation statements)

References 80 publications

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“…Intercellular signaling among different immune cell types of sepsis and sepsis-induced ARDS was calculated by CellCall [ 20 ], which is a toolkit for recognition of intercellular communication networks and internal regulatory signals by combining the expression of ligands/receptors with downstream transcription factor (TF) activities for certain ligand–receptor (LR) pairs. Genes that were expressed in less than 10% of the cells of a certain cell type were excluded in this study.…”

Section: Methodsmentioning

confidence: 99%

Investigating the Intercellular Communication Network of Immune Cell in Acute Respiratory Distress Syndrome with Sepsis

Tao

et al. 2022

Computational and Mathematical Methods in Medicine

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Acute respiratory distress syndrome (ARDS) is recognized as a serious public health issue that results in respiratory failure and high mortality rates. The syndrome is characterized by immune cell aggregation, communication, activation, and alveolar epithelial damage. To elucidate the complex dynamic process of the immune system’s response in ARDS, we construct the intercellular communication network of immune cells in ARDS based on a single-cell RNA sequencing dataset (including three sepsis-induced ARDS patients and four sepsis-only patients). The results show that macrophages relayed most of the intercellular signals (ligand–receptor pairs) in both groups. Many genes related to immune response (IFI44L, ISG, and HLA-DQB1) and biological functions (response to virus, negative regulation of viral life cycle, and response to interferon-beta) were detected via differentially expressed gene analysis of macrophages between the two groups. Deep analysis of the intercellular signals related to the macrophage found that sepsis-induced ARDS harbored distinctive intercellular signals related to chemokine–chemokine receptors (CCL3/4/5−CCR1), which mainly are involved in the disturbance of the STAT family transcription factors (TFs), such as STAT2 and STAT3. These signals and downstream TFs might play key roles in macrophage M1/M2 polarization in the process of sepsis-induced ARDS. This study provides a comprehensive view of the intercellular communication landscape between sepsis and sepsis-induced ARDS and identifies key intercellular communications and TFs involved in sepsis-induced ARDS. We believe that our study provides valuable clues for understanding the immune response mechanisms of ARDS.

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Section: Methodsmentioning

confidence: 99%

Investigating the Intercellular Communication Network of Immune Cell in Acute Respiratory Distress Syndrome with Sepsis

Tao

et al. 2022

Computational and Mathematical Methods in Medicine

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“…For a given signaling pathway, a receiver cell responds to signals from a sender cell by triggering downstream gene responses, including altered transcription factor activity and target gene expression. While most of the existing methods infer intercellular communication based only on expression of ligand-receptor pairs, several methods have recently taken into account the intracellular downstream response in receiver cells [27,[32][33][34][35][36][37] (Figure 1). These methods could reduce false-positive communications by considering the expression of genes for each receptor, transcription factor (TF) and target genes involved in a particular pathway.…”

Section: Computational Approaches For Cell-cell Communication Inferen...mentioning

confidence: 99%

Computational exploration of cellular communication in skin from emerging single-cell and spatial transcriptomic data

Jin

Ramos

2022

Biochemical Society Transactions

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Tissue development and homeostasis require coordinated cell–cell communication. Recent advances in single-cell sequencing technologies have emerged as a revolutionary method to reveal cellular heterogeneity with unprecedented resolution. This offers a great opportunity to explore cell–cell communication in tissues systematically and comprehensively, and to further identify signaling mechanisms driving cell fate decisions and shaping tissue phenotypes. Using gene expression information from single-cell transcriptomics, several computational tools have been developed for inferring cell–cell communication, greatly facilitating analysis and interpretation. However, in single-cell transcriptomics, spatial information of cells is inherently lost. Given that most cell signaling events occur within a limited distance in tissues, incorporating spatial information into cell–cell communication analysis is critical for understanding tissue organization and function. Spatial transcriptomics provides spatial location of cell subsets along with their gene expression, leading to new directions for leveraging spatial information to develop computational approaches for cell–cell communication inference and analysis. These computational approaches have been successfully applied to uncover previously unrecognized mechanisms of intercellular communication within various contexts and across organ systems, including the skin, a formidable model to study mechanisms of cell–cell communication due to the complex interactions between the different cell populations that comprise it. Here, we review emergent cell–cell communication inference tools using single-cell transcriptomics and spatial transcriptomics, and highlight the biological insights gained by applying these computational tools to exploring cellular communication in skin development, homeostasis, disease and aging, as well as discuss future potential research avenues.

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“…However, it has been now shown that immune cells can display pro-or anti-tumour effector functions, with the final outcome being tumour suppression or progression and metastasis, depending on the number, spatiotemporal distribution of relevant immune cells, and the type and/or stage of cancer. Intercellular communication between tumour and immune cells, either through direct cell-cell interactions or the release of soluble cytokines and growth factors, is the basis of mechanisms that tumour cells use to induce tolerance and suppression of anti-tumour responses [117,118]. Adding to this complex scenario, recent studies have highlighted the important role of the metabolic state within the TME [119].…”

Section: The Role Of Citrate On Tumour-infiltrating Immune Cellsmentioning

confidence: 99%

Extracellular citrate and metabolic adaptations of cancer cells

Parkinson

Adamski

Zahn³

et al. 2021

Cancer Metastasis Rev

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It is well established that cancer cells acquire energy via the Warburg effect and oxidative phosphorylation. Citrate is considered to play a crucial role in cancer metabolism by virtue of its production in the reverse Krebs cycle from glutamine. Here, we review the evidence that extracellular citrate is one of the key metabolites of the metabolic pathways present in cancer cells. We review the different mechanisms by which pathways involved in keeping redox balance respond to the need of intracellular citrate synthesis under different extracellular metabolic conditions. In this context, we further discuss the hypothesis that extracellular citrate plays a role in switching between oxidative phosphorylation and the Warburg effect while citrate uptake enhances metastatic activities and therapy resistance. We also present the possibility that organs rich in citrate such as the liver, brain and bones might form a perfect niche for the secondary tumour growth and improve survival of colonising cancer cells. Consistently, metabolic support provided by cancer-associated and senescent cells is also discussed. Finally, we highlight evidence on the role of citrate on immune cells and its potential to modulate the biological functions of pro- and anti-tumour immune cells in the tumour microenvironment. Collectively, we review intriguing evidence supporting the potential role of extracellular citrate in the regulation of the overall cancer metabolism and metastatic activity.

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CellCall: integrating paired ligand–receptor and transcription factor activities for cell–cell communication

Cited by 151 publications

References 80 publications

Investigating the Intercellular Communication Network of Immune Cell in Acute Respiratory Distress Syndrome with Sepsis

Investigating the Intercellular Communication Network of Immune Cell in Acute Respiratory Distress Syndrome with Sepsis

Computational exploration of cellular communication in skin from emerging single-cell and spatial transcriptomic data

Extracellular citrate and metabolic adaptations of cancer cells

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