Single-cell analysis of human skin identifies CD14+ type 3 dendritic cells co-producing IL1B and IL23A in psoriasis

2021 ◽  
Vol 218 (9) ◽  
Author(s):  
Satoshi Nakamizo ◽  
Charles-Antoine Dutertre ◽  
Ahad Khalilnezhad ◽  
Xiao Meng Zhang ◽  
Shawn Lim ◽  
...  
Keyword(s):  
Single Cell ◽  
Skin Diseases ◽  
Single Cell Analysis ◽  
Myeloid Cell ◽  
Molecular Characteristics ◽  
Inflammatory Skin Diseases ◽  
Cell Responses ◽  
Cell Flow Cytometry ◽  
Type 3 ◽  
Macrophage Subsets

Inflammatory skin diseases including atopic dermatitis (AD) and psoriasis (PSO) are underpinned by dendritic cell (DC)–mediated T cell responses. Currently, the heterogeneous human cutaneous DC population is incompletely characterized, and its contribution to these diseases remains unclear. Here, we performed index-sorted single-cell flow cytometry and RNA sequencing of lesional and nonlesional AD and PSO skin to identify macrophages and all DC subsets, including the newly described mature LAMP3+BIRC3+ DCs enriched in immunoregulatory molecules (mregDC) and CD14+ DC3. By integrating our indexed data with published skin datasets, we generated a myeloid cell universe of DC and macrophage subsets in healthy and diseased skin. Importantly, we found that CD14+ DC3s increased in PSO lesional skin and co-produced IL1B and IL23A, which are pathological in PSO. Our study comprehensively describes the molecular characteristics of macrophages and DC subsets in AD and PSO at single-cell resolution, and identifies CD14+ DC3s as potential promoters of inflammation in PSO.

CNS myeloid cell heterogeneity at the single-cell level

Neuroforum ◽  
2019 ◽  
Vol 25 (3) ◽  
pp. 195-204
Author(s):  
Chotima Böttcher ◽  
Roman Sankowski ◽  
Josef Priller ◽  
Marco Prinz
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Myeloid Cell ◽  
Cellular Heterogeneity ◽  
Cell Heterogeneity ◽  
Mass Cytometry ◽  
Dynamic Regulation ◽  
The Central Nervous System ◽  
Disease Profiling ◽  
The Brain

Abstract The cellular composition of the central nervous system (CNS) is highly complex and dynamic. Regulation of this complexity is increasingly recognized to be spatially and temporally dependent during development, homeostasis and disease. Context-dependent cellular heterogeneity was shown for neuroectodermal cells as well as the myeloid compartment of the CNS. The brain myeloid compartment comprises microglia and other CNS-associated macrophages. These are brain-resident cells with critical roles in brain development, maintenance, and immune responses during states of disease. Profiling of CNS myeloid cell heterogeneity has been greatly facilitated in the past years by development of high-throughput technologies for single-cell analysis. This review summarizes current insights into heterogeneity of the CNS myeloid cell population determined by single-cell RNA sequencing and mass cytometry. The results offer invaluable insights into CNS biology and will facilitate the development of therapies for neurodegenerative and neuroinflammatory pathologies.

The single-cell transcriptional landscape of the axolotl

2021 ◽  
Author(s):  
Fang Ye ◽  
Guodong Zhang ◽  
Weigao E ◽  
Haide Chen ◽  
Chengxuan Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Limb Development ◽  
Single Cell Analysis ◽  
Single Cells ◽  
Expression Patterns ◽  
Ambystoma Mexicanum ◽  
System Level ◽  
Molecular Characteristics ◽  
Developmental Studies

Abstract The Mexican axolotl (Ambystoma mexicanum) is a promising tetrapod model for regeneration and developmental studies. Remarkably, neotenic axolotls may undergo metamorphosis, during which their regeneration capacity and lifespan gradually decline. However, a system-level single-cell analysis of molecular characteristics in neotenic and metamorphosed axolotls is still lacking. Here, we developed a single-cell RNA-seq method based on combinatorial hybridization to generate a tissue-based transcriptomic atlas of the adult axolotl. We performed gene expression profiling of over 1 million single cells across 19 tissues to construct the first adult axolotl cell atlas. Comparison of single-cell transcriptomes between the tissues of neotenic and metamorphosed axolotls revealed the heterogeneity of structural cells in different tissues and established their regulatory network. Furthermore, we described dynamic gene expression patterns during limb development in neotenic axolotls. These data serve as a resource to explore the molecular identity of the axolotl as well as its metamorphosis.

scholarly journals Single-cell analysis based dissection of clonality in myelofibrosis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Elena Mylonas ◽  
Kenichi Yoshida ◽  
Mareike Frick ◽  
Kaja Hoyer ◽  
Friederike Christen ◽  
...  
Keyword(s):  
Single Cell ◽  
Recurrent Events ◽  
Somatic Mutations ◽  
Single Cell Analysis ◽  
Clonal Evolution ◽  
Parallel Evolution ◽  
Myeloid Cell ◽  
Clonal Diversity ◽  
Multiple Time ◽  
Over Time

AbstractCancer development is an evolutionary genomic process with parallels to Darwinian selection. It requires acquisition of multiple somatic mutations that collectively cause a malignant phenotype and continuous clonal evolution is often linked to tumor progression. Here, we show the clonal evolution structure in 15 myelofibrosis (MF) patients while receiving treatment with JAK inhibitors (mean follow-up 3.9 years). Whole-exome sequencing at multiple time points reveal acquisition of somatic mutations and copy number aberrations over time. While JAK inhibition therapy does not seem to create a clear evolutionary bottleneck, we observe a more complex clonal architecture over time, and appearance of unrelated clones. Disease progression associates with increased genetic heterogeneity and gain of RAS/RTK pathway mutations. Clonal diversity results in clone-specific expansion within different myeloid cell lineages. Single-cell genotyping of circulating CD34 + progenitor cells allows the reconstruction of MF phylogeny demonstrating loss of heterozygosity and parallel evolution as recurrent events.

Single Cell Analysis of Antigen-Specific T Cell Responses in HIV-Infected Individuals

1999 ◽  
Vol 192 (2) ◽  
pp. 107-112 ◽  
Author(s):  
Baudouin Byl ◽  
Michéle Gérard ◽  
Myriam Libin ◽  
Nathan Clumeck ◽  
Michel Goldman ◽  
...  
Keyword(s):  
T Cell ◽  
Single Cell ◽  
Single Cell Analysis ◽  
T Cell Responses ◽  
Cell Analysis ◽  
Cell Responses

scholarly journals Highly Efficient, Massively-Parallel Single-Cell RNA-Seq Reveals Cellular States and Molecular Features of Human Skin Pathology

2019 ◽  
Author(s):  
Travis K Hughes ◽  
Marc H Wadsworth ◽  
Todd M Gierahn ◽  
Tran Do ◽  
David Weiss ◽  
...  
Keyword(s):  
Single Cell ◽  
Human Skin ◽  
Skin Diseases ◽  
Parenchymal Cell ◽  
Skin Inflammation ◽  
Microtiter Plate ◽  
Massively Parallel ◽  
Inflammatory Skin Diseases ◽  
Molecular Features ◽  
Methodological Advance

SUMMARYThe development of high-throughput single-cell RNA-sequencing (scRNA-Seq) methodologies has empowered the characterization of complex biological samples by dramatically increasing the number of constituent cells that can be examined concurrently. Nevertheless, these approaches typically recover substantially less information per-cell as compared to lower-throughput microtiter plate-based strategies. To uncover critical phenotypic differences among cells and effectively link scRNA-Seq observations to legacy datasets, reliable detection of phenotype-defining transcripts – such as transcription factors, affinity receptors, and signaling molecules – by these methods is essential. Here, we describe a substantially improved massively-parallel scRNA-Seq protocol we term Seq-Well S^3 (“Second-Strand Synthesis”) that increases the efficiency of transcript capture and gene detection by up to 10- and 5-fold, respectively, relative to previous iterations, surpassing best-in-class commercial analogs. We first characterized the performance of Seq-Well S^3 in cell lines and PBMCs, and then examined five different inflammatory skin diseases, illustrative of distinct types of inflammation, to explore the breadth of potential immune and parenchymal cell states. Our work presents an essential methodological advance as well as a valuable resource for studying the cellular and molecular features that inform human skin inflammation.

Single-Cell Analysis Of Allergen-specific T cell Responses with MHC-class II peptide tetramers

2008 ◽  
Vol 121 (2) ◽  
pp. S211-S211
Author(s):  
E WAMBRE ◽  
L VANOVERTVELT ◽  
B MAILLERE ◽  
R HUMPHREYS ◽  
E VANHOFE ◽  
...  
Keyword(s):  
T Cell ◽  
Single Cell ◽  
Mhc Class Ii ◽  
Single Cell Analysis ◽  
T Cell Responses ◽  
Class Ii ◽  
Cell Analysis ◽  
Cell Responses

In situ High-Throughput Single-Cell Analysis Reveals the Crosstalk between Nanoparticle-Induced Cell Responses

2021 ◽  
Vol 55 (8) ◽  
pp. 5136-5142
Author(s):  
Yuanyuan Wang ◽  
Fengbang Wang ◽  
Zihan Chen ◽  
Maoyong Song ◽  
Xinglei Yao ◽  
...  
Keyword(s):  
Single Cell ◽  
High Throughput ◽  
Single Cell Analysis ◽  
Cell Analysis ◽  
Cell Responses

Stat3 is activated in skin lesions by the local application of imiquimod, a ligand of TLR7, and inhibited by the recombinant peptide aptamer rS3-PA

2012 ◽  
Vol 10 (2) ◽  
Author(s):  
Laura Mack ◽  
Boris Brill ◽  
Natalia Delis ◽  
Corina Borghouts ◽  
Axel Weber ◽  
...  
Keyword(s):  
Skin Diseases ◽  
Cultured Cells ◽  
Mouse Skin ◽  
Skin Lesions ◽  
Molecular Characteristics ◽  
T Helper 17 ◽  
Inflammatory Skin Diseases ◽  
Recombinant Peptide ◽  
Peptide Aptamer ◽  
Inflammatory Autoimmune Disease

AbstractSignal transducer and activator of transcription 3 (Stat3) assumes central functions in the regulation of apoptosis, proliferation, angiogenesis, and immune responses in normal cells. It also plays crucial roles in inflammatory and malignant diseases and in the cellular communication in the tissue microenvironment. Signaling interactions among normal endothelial cells, immune cells, and tumor cells, mediated by the release of cytokines, chemokines, and growth factors, often result in the activation of Stat3 and promotion of cancer cell proliferation, invasion, angiogenesis, and immune evasion. Stat3 also causes the differentiation and activation of T helper 17 (Th17) cells, which is involved, e.g., in psoriasis, an inflammatory autoimmune disease of the skin. Here, we describe molecular characteristics of a mouse model triggered by the treatment of mouse skin with the immune modulator imiquimod. The application of this compound causes the local release of proinflammatory cytokines and symptoms that resemble human psoriasis. We show that this process is accompanied by strong Stat3 activation. We also investigated the effects of a membrane-permeable, peptide-based Stat3 inhibitor, recombinant Stat3-specific peptide aptamer (rS3-PA). This molecule specifically interacts with Stat3 and prevents its transactivation potential in cultured cells. rS3-PA is able to penetrate the skin, enter cells, and reduce the level of activated Stat3. The topical applications of rS3-PA to the skin could thus possibly become useful in the treatment of inflammatory skin diseases and skin cancer.

Sign in / Sign up

Export Citation Format

Share Document