scholarly journals Transfer of extracellular vesicles during immune cell-cell interactions

2012 ◽  
Vol 251 (1) ◽  
pp. 125-142 ◽  
Author(s):  
Cristina Gutiérrez-Vázquez ◽  
Carolina Villarroya-Beltri ◽  
María Mittelbrunn ◽  
Francisco Sánchez-Madrid
2021 ◽  
Author(s):  
Rob C. Oslund ◽  
Tamara Reyes-Robles ◽  
Cory H. White ◽  
Jake H. Tomlinson ◽  
Kelly A. Crotty ◽  
...  

AbstractCell-cell interactions drive essential biological processes critical to cell and tissue development, function, pathology, and disease outcome. The growing appreciation of immune cell interactions within disease environments has led to significant efforts to develop protein- and cell-based therapeutic strategies. A better understanding of these cell-cell interactions will enable the development of effective immunotherapies. However, characterizing these complex cellular interactions at molecular resolution in their native biological contexts remains challenging. To address this, we introduce photocatalytic cell tagging (PhoTag), a modality agnostic platform for profiling cell-cell interactions. Using photoactivatable flavin-based cofactors, we generate phenoxy radical tags for targeted labeling at the cell surface. Through various targeting modalities (e.g. MHC-Multimer, antibody, single domain antibody (VHH)) we deliver a flavin photocatalyst for cell tagging within monoculture, co-culture, and peripheral blood mononuclear cells. PhoTag enables highly selective tagging of the immune synapse between an immune cell and an antigen-presenting cell through targeted labeling at the cell-cell junction. This allowed for the ability to profile gene expression-level differences between interacting and bystander cell populations. Given the modality agnostic and spatio-temporal nature of PhoTag, we envision its broad utilization to detect and profile intercellular interactions within an immune synapse and other confined cellular regions for any biological system.


Author(s):  
E. Bustos-Morán ◽  
N. Blas-Rus ◽  
N.B. Martín-Cófreces ◽  
F. Sánchez-Madrid

2021 ◽  
Author(s):  
Bianca C.T Flores ◽  
Smriti Chawla ◽  
Ning Ma ◽  
Chad Sanada ◽  
Praveen Kumar Kujur ◽  
...  

Cell-cell communication and physical interactions play a vital role in cancer initiation, homeostasis, progression, and immune response. Here, we report a system that combines live capture of different cell types, co-incubation, time-lapse imaging, and gene expression profiling of doublets using a microfluidic integrated fluidic circuit (IFC) that enables measurement of physical distances between cells and the associated transcriptional profiles due to cell-cell interactions. The temporal variations in natural killer (NK) - triple-negative breast cancer (TNBC) cell distances were tracked and compared with terminally profiled cellular transcriptomes. The results showed the time-bound activities of regulatory modules and alluded to the existence of transcriptional memory. Our experimental and bioinformatic approaches serve as a proof of concept for interrogating live cell interactions at doublet resolution, which can be applied across different cancers and cell types.


2020 ◽  
Author(s):  
Daniel Li ◽  
Qiang Ma ◽  
Jennifer Chen ◽  
Andrew Liu ◽  
Justin Cheung ◽  
...  

AbstractRecent multiplexed protein imaging technologies make it possible to characterize cells, their spatial organization, and interactions within microenvironments at unprecedented resolution. Although observational data can reveal spatial associations, it does not allow users to infer biologically causative relationships and interactions between cells. To address this challenge, we develop a generative model that allows users to test hypotheses about the effect of cell-cell interactions on protein expression through in silico perturbation. Our Cell-Cell Interaction GAN (CCIGAN) model employs a generative adversarial network (GAN) architecture to generate biologically realistic multiplexed cell images from semantic cell segmentations. Our approach is unique in considering all imaging channels simultaneously, and we show that it successfully captures known tumor-immune cell interactions missed by other state-of-the-art GAN models, and yields biological insights without requiring in vivo manipulation. CCIGAN accepts data from multiple imaging technologies and can infer interactions from single images in any health or disease context.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Cornelius H. L. Kürten ◽  
Aditi Kulkarni ◽  
Anthony R. Cillo ◽  
Patricia M. Santos ◽  
Anna K. Roble ◽  
...  

AbstractHead and neck squamous cell carcinoma (HNSCC) is characterized by complex relations between stromal, epithelial, and immune cells within the tumor microenvironment (TME). To enable the development of more efficacious therapies, we aim to study the heterogeneity, signatures of unique cell populations, and cell-cell interactions of non-immune and immune cell populations in 6 human papillomavirus (HPV)+ and 12 HPV– HNSCC patient tumor and matched peripheral blood specimens using single-cell RNA sequencing. Using this dataset of 134,606 cells, we show cell type-specific signatures associated with inflammation and HPV status, describe the negative prognostic value of fibroblasts with elastic differentiation specifically in the HPV+ TME, predict therapeutically targetable checkpoint receptor-ligand interactions, and show that tumor-associated macrophages are dominant contributors of PD-L1 and other immune checkpoint ligands in the TME. We present a comprehensive single-cell view of cell-intrinsic mechanisms and cell-cell communication shaping the HNSCC microenvironment.


2019 ◽  
Vol 20 (24) ◽  
pp. 6178 ◽  
Author(s):  
Kelli Gerth ◽  
Sunitha Kodidela ◽  
Madeline Mahon ◽  
Sanjana Haque ◽  
Neha Verma ◽  
...  

The cytochrome P450 (CYP) family of enzymes is known to metabolize the majority of xenobiotics. Hepatocytes, powerhouses of CYP enzymes, are where most drugs are metabolized into non-toxic metabolites. Additional tissues/cells such as gut, kidneys, lungs, blood, and brain cells express selective CYP enzymes. Extrahepatic CYP enzymes, especially in kidneys, also metabolize drugs into excretable forms. However, extrahepatic cells express a much lower level of CYPs than hepatocytes. It is possible that the liver secretes CYP enzymes, which circulate via plasma and are eventually delivered to extrahepatic cells (e.g., brain cells). CYP circulation likely occurs via extracellular vesicles (EVs), which carry important biomolecules for delivery to distant cells. Recent studies have revealed an abundance of several CYPs in plasma EVs and other cell-derived EVs, and have demonstrated the role of CYP-containing EVs in xenobiotic-induced toxicity via cell–cell interactions. Thus, it is important to study the mechanism for packaging CYP into EVs, their circulation via plasma, and their role in extrahepatic cells. Future studies could help to find novel EV biomarkers and help to utilize EVs in novel interventions via CYP-containing EV drug delivery. This review mainly covers the abundance of CYPs in plasma EVs and EVs derived from CYP-expressing cells, as well as the potential role of EV CYPs in cell–cell communication and their application with respect to novel biomarkers and therapeutic interventions.


2021 ◽  
Author(s):  
Bianca Flores ◽  
Smriti Chawla ◽  
Ning Ma ◽  
Chad Sanada ◽  
Praveen Kujur ◽  
...  

Abstract Cell-cell communication and physical interactions play a vital role in cancer initiation, homeostasis, progression, and immune response. Here, we report a system that combines live capture of different cell types, co-incubation, time-lapse imaging, and gene expression profiling of doublets using a microfluidic integrated fluidic circuit (IFC) that enables measurement of physical distances between cells and the associated transcriptional profiles due to cell-cell interactions. The temporal variations in natural killer (NK) - triple-negative breast cancer (TNBC) cell distances were tracked and compared with terminally profiled cellular transcriptomes. The results showed the time-bound activities of regulatory modules and alluded to the existence of transcriptional memory. Our experimental and bioinformatic approaches serve as a proof of concept for interrogating live cell interactions at doublet resolution, which can be applied across different cancers and cell types.


Sign in / Sign up

Export Citation Format

Share Document