scholarly journals Single-cell biology to decode the immune cellular composition of kidney inflammation

2021 ◽  
Author(s):  
Yu Zhao ◽  
Ulf Panzer ◽  
Stefan Bonn ◽  
Christian F. Krebs
Keyword(s):  
Single Cell ◽  
Cell Biology ◽  
Computational Analysis ◽  
Immune Cell ◽  
Therapeutic Interventions ◽  
Experimental Setup ◽  
Disease Etiology ◽  
Rna Profiling ◽  
Immune Mediated ◽  
Health And Disease

AbstractSingle-cell biology is transforming the ability of researchers to understand cellular signaling and identity across medical and biological disciplines. Especially for immune-mediated diseases, a single-cell look at immune cell subtypes, signaling, and activity might yield fundamental insights into the disease etiology, mechanisms, and potential therapeutic interventions. In this review, we highlight recent advances in the field of single-cell RNA profiling and their application to understand renal function in health and disease. With a focus on the immune system, in particular on T cells, we propose some key directions of understanding renal inflammation using single-cell approaches. We detail the benefits and shortcomings of the various technological approaches outlined and give advice on potential pitfalls and challenges in experimental setup and computational analysis. Finally, we conclude with a brief outlook into a promising future for single-cell technologies to elucidate kidney function.

scholarly journals Melanoma Single-Cell Biology in Experimental and Clinical Settings

2021 ◽  
Vol 10 (3) ◽  
pp. 506
Author(s):  
Hans Binder ◽  
Maria Schmidt ◽  
Henry Loeffler-Wirth ◽  
Lena Suenke Mortensen ◽  
Manfred Kunz
Keyword(s):  
T Cell ◽  
Single Cell ◽  
Intracellular Signaling ◽  
Cell Biology ◽  
Immune Cell ◽  
Malignant Tumors ◽  
Checkpoint Inhibitor ◽  
Treatment Resistance ◽  
Resistance Mechanisms ◽  
Cellular Heterogeneity

Cellular heterogeneity is regarded as a major factor for treatment response and resistance in a variety of malignant tumors, including malignant melanoma. More recent developments of single-cell sequencing technology provided deeper insights into this phenomenon. Single-cell data were used to identify prognostic subtypes of melanoma tumors, with a special emphasis on immune cells and fibroblasts in the tumor microenvironment. Moreover, treatment resistance to checkpoint inhibitor therapy has been shown to be associated with a set of differentially expressed immune cell signatures unraveling new targetable intracellular signaling pathways. Characterization of T cell states under checkpoint inhibitor treatment showed that exhausted CD8+ T cell types in melanoma lesions still have a high proliferative index. Other studies identified treatment resistance mechanisms to targeted treatment against the mutated BRAF serine/threonine protein kinase including repression of the melanoma differentiation gene microphthalmia-associated transcription factor (MITF) and induction of AXL receptor tyrosine kinase. Interestingly, treatment resistance mechanisms not only included selection processes of pre-existing subclones but also transition between different states of gene expression. Taken together, single-cell technology has provided deeper insights into melanoma biology and has put forward our understanding of the role of tumor heterogeneity and transcriptional plasticity, which may impact on innovative clinical trial designs and experimental approaches.

scholarly journals The New Old CD8+ T Cells in the Immune Paradox of Pregnancy

2021 ◽  
Vol 12 ◽  
Author(s):  
Lilja Hardardottir ◽  
Maria Victoria Bazzano ◽  
Laura Glau ◽  
Luca Gattinoni ◽  
Angela Köninger ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Biology ◽  
Immune Cell ◽  
Cd8 T Cell ◽  
Therapeutic Interventions ◽  
Effector Memory ◽  
Pregnant Uterus ◽  
T Cell Biology

CD8+ T cells are the most frequent T cell population in the immune cell compartment at the feto-maternal interface. Due to their cytotoxic potential, the presence of CD8+ T cells in the immune privileged pregnant uterus has raised considerable interest. Here, we review our current understanding of CD8+ T cell biology in the uterus of pregnant women and discuss this knowledge in relation to a recently published immune cell Atlas of human decidua. We describe how the expansion of CD8+ T cells with an effector memory phenotype often presenting markers of exhaustion is critical for a successful pregnancy, and host defense towards pathogens. Moreover, we review new evidence on the presence of long-lasting immunological memory to former pregnancies and discuss its impact on prospective pregnancy outcomes. The formation of fetal-specific memory CD8+ T cell subests in the uterus, in particular of tissue resident, and stem cell memory cells requires further investigation, but promises interesting results to come. Advancing the knowledge of CD8+ T cell biology in the pregnant uterus will be pivotal for understanding not only tissue-specific immune tolerance but also the etiology of complications during pregnancy, thus enabling preventive or therapeutic interventions in the future.

scholarly journals Heterogeneity of Circulating Tumor Cell Neoplastic Subpopulations Outlined by Single-Cell Transcriptomics

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4885
Author(s):  
Christine M. Pauken ◽  
Shelby Ray Kenney ◽  
Kathryn J. Brayer ◽  
Yan Guo ◽  
Ursa A. Brown-Glaberman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Immune Cell ◽  
Metastatic Breast ◽  
Gene Expression Signature ◽  
Circulating Tumor Cell ◽  
Therapeutic Interventions ◽  
Cell Populations ◽  
Breast Cancer Patients ◽  
The Common

Fatal metastasis occurs when circulating tumor cells (CTCs) disperse through the blood to initiate a new tumor at specific sites distant from the primary tumor. CTCs have been classically defined as nucleated cells positive for epithelial cell adhesion molecule and select cytokeratins (EpCAM/CK/DAPI), while negative for the common lymphocyte marker CD45. The enumeration of CTCs allows an estimation of the overall metastatic burden in breast cancer patients, but challenges regarding CTC heterogeneity and metastatic propensities persist, and their decryption could improve therapies. CTCs from metastatic breast cancer (mBC) patients were captured using the RareCyteTM Cytefinder II platform. The Lin− and Lin+ (CD45+) cell populations isolated from the blood of three of these mBC patients were analyzed by single-cell transcriptomic methods, which identified a variety of immune cell populations and a cluster of cells with a distinct gene expression signature, which includes both cells expressing EpCAM/CK (“classic” CTCs) and cells possessing an array of genes not previously associated with CTCs. This study put forward notions that the identification of these genes and their interactions will promote novel areas of analysis by dissecting properties underlying CTC survival, proliferation, and interaction with circulatory immune cells. It improves upon capabilities to measure and interfere with CTCs for impactful therapeutic interventions.

scholarly journals Multiplexed Single-Cell in situ RNA Profiling

2021 ◽  
Vol 8 ◽  
Author(s):  
Yu-Sheng Wang ◽  
Jia Guo
Keyword(s):  
Single Cell ◽  
Single Cells ◽  
Disease Diagnosis ◽  
Tissue Architecture ◽  
Rna Profiling ◽  
Rna Analysis ◽  
Technological Advances ◽  
Health And Disease ◽  
Type Classification

The ability to quantify a large number of varied transcripts in single cells in their native spatial context is crucial to accelerate our understanding of health and disease. Bulk cell RNA analysis masks the heterogeneity in the cell population, while the conventional RNA imaging approaches suffer from low multiplexing capacity. Recent advances in multiplexed fluorescence in situ hybridization (FISH) methods enable comprehensive RNA profiling in individual cells in situ. These technologies will have wide applications in many biological and biomedical fields, including cell type classification, signaling network analysis, tissue architecture, disease diagnosis and patient stratification, etc. In this minireview, we will present the recent technological advances of multiplexed single-cell in situ RNA profiling assays, discuss their advantages and limitations, describe their biological applications, highlight the current challenges, and propose potential solutions.

scholarly journals Single cell transcriptional profiling reveals cellular diversity, communication, and sexual dimorphism in the mouse heart

2017 ◽  
Author(s):  
Daniel A. Skelly ◽  
Galen T. Squiers ◽  
Micheal A. McLellan ◽  
Mohan T. Bolisetty ◽  
Paul Robson ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Single Cell ◽  
Cell Biology ◽  
Immune Cell ◽  
Cardiac Development ◽  
Transcriptional Profiling ◽  
Cell Populations ◽  
Mouse Heart ◽  
Cardiac Cell ◽  
Immune Sensing

INTRODUCTORY PARAGRAPHCharacterization of the cardiac cellulome—the network of cells that form the heart—is essential for understanding cardiac development and normal organ function, and for formulating precise therapeutic strategies to combat heart disease. Recent studies have challenged assumptions about both the cellular composition1 and functional significance of the cardiac non-myocyte cell pool, with unexpected roles identified for resident fibroblasts2 and immune cell populations3,4. In this study, we characterized single-cell transcriptional profiles of the murine non-myocyte cardiac cellular landscape using single-cell RNA sequencing (scRNA-Seq). Detailed molecular analyses revealed the diversity of the cardiac cellulome and facilitated the development of novel techniques to isolate understudied cardiac cell populations such as mural cells and glia. Our analyses also revealed networks of intercellular communication as well as extensive sexual dimorphism in gene expression in the heart, most notably demonstrated by the upregulation of immune-sensing and pro-inflammatory genes in male cardiac macrophages. This study offers new insights into the structure and function of the mammalian cardiac cellulome and provides an important resource that will stimulate new studies in cardiac cell biology.

scholarly journals Immune cell dynamics induced by a single dose of pembrolizumab as revealed by single-cell RNA profiling

2019 ◽  
Vol 30 ◽  
pp. iii45
Author(s):  
H. Vos ◽  
A. Bassez ◽  
J. Qian ◽  
G. Floris ◽  
I. Nevelsteen ◽  
...  
Keyword(s):  
Single Dose ◽  
Single Cell ◽  
Immune Cell ◽  
Cell Dynamics ◽  
Rna Profiling

scholarly journals Single-cell analysis of mosquito hemocytes identifies signatures of immune cell sub-types and cell differentiation

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Hyeogsun Kwon ◽  
Mubasher Mohammed ◽  
Oscar Franzén ◽  
Johan Ankarklev ◽  
Ryan Smith
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Immune Cells ◽  
Cell Biology ◽  
Immune Cell ◽  
Single Cell Analysis ◽  
Immune Priming ◽  
Rna Fish ◽  
Invertebrate Immunology ◽  
Humoral Responses

Mosquito immune cells, known as hemocytes, are integral to cellular and humoral responses that limit pathogen survival and mediate immune priming. However, without reliable cell markers and genetic tools, studies of mosquito immune cells have been limited to morphological observations, leaving several aspects of their biology uncharacterized. Here, we use single-cell RNA sequencing (scRNA-seq) to characterize mosquito immune cells, demonstrating an increased complexity to previously defined prohemocyte, oenocytoid, and granulocyte subtypes. Through functional assays relying on phagocytosis, phagocyte depletion, and RNA-FISH experiments, we define markers to accurately distinguish immune cell subtypes and provide evidence for immune cell maturation and differentiation. In addition, gene-silencing experiments demonstrate the importance of lozenge in defining the mosquito oenocytoid cell fate. Together, our scRNA-seq analysis provides an important foundation for future studies of mosquito immune cell biology and a valuable resource for comparative invertebrate immunology.

scholarly journals Deep spatial profiling of COVID19 brains reveals neuroinflammation by compartmentalized local immune cell interactions and targets for intervention

2020 ◽  
Author(s):  
Bertram Bengsch ◽  
Marius Schwabenland ◽  
Henrike Salié ◽  
Jovan Tanevski ◽  
Saskia Killmer ◽  
...  
Keyword(s):  
Immune Response ◽  
Single Cell ◽  
Immune Cell ◽  
Single Cell Analysis ◽  
Therapeutic Interventions ◽  
Immune Checkpoints ◽  
Structural Basis ◽  
Cellular Interactions ◽  
Local Immune Response ◽  
Spatially Resolved

Abstract COVID-19 causes neurological symptoms that can be potentially life-threatening in up to 67 % of the patients. The underlying pathophysiological mechanisms of COVID-19 associated encephalopathy, the involved immune cells, their spatial distribution and their cellular interactions during disease remain largely unclear. In this study, we performed a 38-biomarker imaging mass cytometry analysis of the brain stem from 25 patients and additional controls to understand the local immune response during SARS-CoV-2 infection at a spatially resolved, high-dimensional single-cell level. Importantly, utilizing an unbiased image segmentation and cell classification pipeline, we observed a significant immune activation in the central nervous system (CNS) and identified novel context-specific CD8 T cell and microglial clusters. Spatially resolved single-cell analysis identified distinct phenotypes of T cells and microglial clusters, their presence in specific anatomical regions and their cellular interactions. Our analysis further highlights microglial nodules and perivascular immune cell clusters as key sites of the local immune response. It also demonstrates that disease-associated neuroinflammation is associated with severe axonal damage as a structural basis for the neurologic deficits. Finally, we identified compartment- and cluster-specific immune checkpoints that can be used for future therapeutic interventions.

scholarly journals Deciphering Cell Fate Decision by Integrated Single-Cell Sequencing Analysis

2020 ◽  
Vol 3 (1) ◽  
pp. 1-22 ◽  
Author(s):  
Sagar ◽  
Dominic Grün
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Cell Biology ◽  
Cellular Differentiation ◽  
Sequencing Analysis ◽  
Cell Fate Decision ◽  
Modern Biology ◽  
Health And Disease ◽  
Fate Decision ◽  
Multicellular Organisms

Cellular differentiation is a common underlying feature of all multicellular organisms through which naïve cells progressively become fate restricted and develop into mature cells with specialized functions. A comprehensive understanding of the regulatory mechanisms of cell fate choices during development, regeneration, homeostasis, and disease is a central goal of modern biology. Ongoing rapid advances in single-cell biology are enabling the exploration of cell fate specification at unprecedented resolution. Here, we review single-cell RNA sequencing and sequencing of other modalities as methods to elucidate the molecular underpinnings of lineage specification. We specifically discuss how the computational tools available to reconstruct lineage trajectories, quantify cell fate bias, and perform dimensionality reduction for data visualization are providing new mechanistic insights into the process of cell fate decision. Studying cellular differentiation using single-cell genomic tools is paving the way for a detailed understanding of cellular behavior in health and disease.

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