scholarly journals Dynamic changes in the regulatory T cell heterogeneity and function by murine IL-2 mutein

2019 ◽  
Author(s):  
Daniel R. Lu ◽  
Hao Wu ◽  
Ian Driver ◽  
Sarah Ingersoll ◽  
Sue Sohn ◽  
...  
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Expression Profiles ◽  
Control Cell ◽  
Mutant Form ◽  
Cell Analysis ◽  
Suppressive Function ◽  
Cell Clustering ◽  
Transcriptional Changes ◽  
And Function

AbstractThe therapeutic expansion of Foxp3+ regulatory T cells (Tregs) shows promise for treating autoimmune and inflammatory disorders. Yet, how this treatment affects the heterogeneity and function of Tregs is not clear. Using single-cell RNA-seq analysis, we characterized 31,908 Tregs from the mice treated with a half-life extended mutant form of murine IL-2 (IL-2 mutein, IL-2M) that preferentially expanded Tregs, or mouse IgG Fc as a control. Cell clustering analysis revealed that IL-2M specifically expands multiple sub-states of Tregs with distinct expression profiles. TCR-profiling with single-cell analysis uncovered Treg migration across tissues and transcriptional changes between clonally related Tregs following IL-2M treatment. Finally, we identified IL-2M-expanded Tnfrsf9+Il1rl1+ Tregs with superior suppressive function, highlighting the potential of IL-2M to expand highly suppressive Foxp3+ Tregs.One Sentence SummarySingle-cell analysis revealed that IL-2 mutein treatment expanded multiple sub-states of Tregs with a highly suppressive function in mice.

scholarly journals Dynamic changes in the regulatory T-cell heterogeneity and function by murine IL-2 mutein

2020 ◽  
Vol 3 (5) ◽  
pp. e201900520 ◽  
Author(s):  
Daniel R Lu ◽  
Hao Wu ◽  
Ian Driver ◽  
Sarah Ingersoll ◽  
Sue Sohn ◽  
...  
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Expression Profiles ◽  
Control Cell ◽  
Mutant Form ◽  
Rna Seq ◽  
Dynamic Changes ◽  
Cell Clustering ◽  
Transcriptional Changes ◽  
And Function

The therapeutic expansion of Foxp3+ regulatory T cells (Tregs) shows promise for treating autoimmune and inflammatory disorders. Yet, how this treatment affects the heterogeneity and function of Tregs is not clear. Using single-cell RNA-seq analysis, we characterized 31,908 Tregs from the mice treated with a half-life extended mutant form of murine IL-2 (IL-2 mutein, IL-2M) that preferentially expanded Tregs, or mouse IgG Fc as a control. Cell clustering analysis revealed that IL-2M specifically expands multiple sub-states of Tregs with distinct expression profiles. TCR profiling with single-cell analysis uncovered Treg migration across tissues and transcriptional changes between clonally related Tregs after IL-2M treatment. Finally, we identified IL-2M–expanded Tnfrsf9+Il1rl1+ Tregs with superior suppressive function, highlighting the potential of IL-2M to expand highly suppressive Foxp3+ Tregs.

scholarly journals Single-Cell Analysis of Antigen-Specific CD8+ T-Cell Transcripts Reveals Profiles Specific to mRNA or Adjuvanted Protein Vaccines

2021 ◽  
Vol 12 ◽  
Author(s):  
Trine Sundebo Meldgaard ◽  
Fabiola Blengio ◽  
Denise Maffione ◽  
Chiara Sammicheli ◽  
Simona Tavarini ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Cd8 T Cells ◽  
Single Cell Analysis ◽  
Expression Profiles ◽  
Cd8 T Cell ◽  
Cellular Heterogeneity ◽  
Cell Analysis

CD8+ T cells play a key role in mediating protective immunity after immune challenges such as infection or vaccination. Several subsets of differentiated CD8+ T cells have been identified, however, a deeper understanding of the molecular mechanism that underlies T-cell differentiation is lacking. Conventional approaches to the study of immune responses are typically limited to the analysis of bulk groups of cells that mask the cells’ heterogeneity (RNA-seq, microarray) and to the assessment of a relatively limited number of biomarkers that can be evaluated simultaneously at the population level (flow and mass cytometry). Single-cell analysis, on the other hand, represents a possible alternative that enables a deeper characterization of the underlying cellular heterogeneity. In this study, a murine model was used to characterize immunodominant hemagglutinin (HA533-541)-specific CD8+ T-cell responses to nucleic- and protein-based influenza vaccine candidates, using single-cell sorting followed by transcriptomic analysis. Investigation of single-cell gene expression profiles enabled the discovery of unique subsets of CD8+ T cells that co-expressed cytotoxic genes after vaccination. Moreover, this method enabled the characterization of antigen specific CD8+ T cells that were previously undetected. Single-cell transcriptome profiling has the potential to allow for qualitative discrimination of cells, which could lead to novel insights on biological pathways involved in cellular responses. This approach could be further validated and allow for more informed decision making in preclinical and clinical settings.

scholarly journals Single-cell analysis reveals a nestin+ tendon stem/progenitor cell population with strong tenogenic potentiality

2016 ◽  
Vol 2 (11) ◽  
pp. e1600874 ◽  
Author(s):  
Zi Yin ◽  
Jia-jie Hu ◽  
Long Yang ◽  
Ze-Feng Zheng ◽  
Cheng-rui An ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Cell Population ◽  
Single Cell Analysis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Analysis ◽  
Nestin Expression

The repair of injured tendons remains a formidable clinical challenge because of our limited understanding of tendon stem cells and the regulation of tenogenesis. With single-cell analysis to characterize the gene expression profiles of individual cells isolated from tendon tissue, a subpopulation of nestin+ tendon stem/progenitor cells (TSPCs) was identified within the tendon cell population. Using Gene Expression Omnibus datasets and immunofluorescence assays, we found that nestin expression was activated at specific stages of tendon development. Moreover, isolated nestin+ TSPCs exhibited superior tenogenic capacity compared to nestin− TSPCs. Knockdown of nestin expression in TSPCs suppressed their clonogenic capacity and reduced their tenogenic potential significantly both in vitro and in vivo. Hence, these findings provide new insights into the identification of subpopulations of TSPCs and illustrate the crucial roles of nestin in TSPC fate decisions and phenotype maintenance, which may assist in future therapeutic strategies to treat tendon disease.

scholarly journals Mitochondrial isolation: when size matters

2020 ◽  
Vol 5 ◽  
pp. 226
Author(s):  
Alexander G. Bury ◽  
Amy E. Vincent ◽  
Doug M. Turnbull ◽  
Paolo Actis ◽  
Gavin Hudson
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Cellular Heterogeneity ◽  
Cell Analysis ◽  
Cell Level ◽  
Isolation Techniques ◽  
Cellular Environment ◽  
Dynamics And Function ◽  
And Function ◽  
Subcellular Resolution

Mitochondrial vitality is critical to cellular function, with mitochondrial dysfunction linked to a growing number of human diseases. Tissue and cellular heterogeneity, in terms of genetics, dynamics and function means that increasingly mitochondrial research is conducted at the single cell level. Whilst there are several technologies that are currently available for single-cell analysis, each with their advantages, they cannot be easily adapted to study mitochondria with subcellular resolution. Here we review the current techniques and strategies for mitochondrial isolation, critically discussing each technology’s limitations for future mitochondrial research. Finally, we highlight and discuss the recent breakthroughs in sub-cellular isolation techniques, with a particular focus on nanotechnologies that enable the isolation of mitochondria from subcellular compartments. This allows isolation of mitochondria with unprecedented spatial precision with minimal disruption to mitochondria and their immediate cellular environment.

scholarly journals 331 Single cell analysis reveals diversity of phenotype and function of autoantigen-specific B cells in systemic sclerosis

2017 ◽  
Vol 137 (10) ◽  
pp. S249
Author(s):  
A. Yoshizaki ◽  
T. Fukasawa ◽  
S. Ebata ◽  
Y. Asano ◽  
K. Mawatari ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
B Cells ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Cell Analysis ◽  
And Function

scholarly journals ArchR is a scalable software package for integrative single-cell chromatin accessibility analysis

2021 ◽  
Vol 53 (3) ◽  
pp. 403-411 ◽  
Author(s):  
Jeffrey M. Granja ◽  
M. Ryan Corces ◽  
Sarah E. Pierce ◽  
S. Tansu Bagdatli ◽  
Hani Choudhry ◽  
...  
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Single Cells ◽  
Chromatin Accessibility ◽  
Cell Analysis ◽  
Software Suite ◽  
Cell Clustering ◽  
Gene Regulatory ◽  
Regulatory Landscapes ◽  
Scalable Software

AbstractThe advent of single-cell chromatin accessibility profiling has accelerated the ability to map gene regulatory landscapes but has outpaced the development of scalable software to rapidly extract biological meaning from these data. Here we present a software suite for single-cell analysis of regulatory chromatin in R (ArchR; https://www.archrproject.com/) that enables fast and comprehensive analysis of single-cell chromatin accessibility data. ArchR provides an intuitive, user-focused interface for complex single-cell analyses, including doublet removal, single-cell clustering and cell type identification, unified peak set generation, cellular trajectory identification, DNA element-to-gene linkage, transcription factor footprinting, mRNA expression level prediction from chromatin accessibility and multi-omic integration with single-cell RNA sequencing (scRNA-seq). Enabling the analysis of over 1.2 million single cells within 8 h on a standard Unix laptop, ArchR is a comprehensive software suite for end-to-end analysis of single-cell chromatin accessibility that will accelerate the understanding of gene regulation at the resolution of individual cells.

Author response for "Immunocyte single cell analysis of vaccine‐induced narcolepsy"

2020 ◽  
Author(s):  
Alexander Lind ◽  
Falastin Salami ◽  
Anne‐Marie Landtblom ◽  
Lars Palm ◽  
Åke Lernmark ◽  
...  
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Author Response ◽  
Cell Analysis
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