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Single-cell transcriptomics in human skin research: available technologies, technical considerations and disease applications

EXPERIMENTAL DERMATOLOGY (2022)

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Summary: This study describes a new workflow for isolating and expanding significant amounts of T cells from fetal human skin. The characteristics of T cells in fetal skin were determined using multiparametric flow cytometry and immunofluorescence techniques. The molecular state of these cells was characterized using single-cell transcriptomics and TCR repertoire profiling.

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Article Dermatology

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Summary: In this study, single-cell RNA sequencing and spatial transcriptomics were used to uncover the underlying pathophysiology of keloids. The results revealed cellular heterogeneity, cell-cell interactions, and mesenchymal activation of endothelial cells, which may play a role in the development of keloids.

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Single cell transcriptomic landscape of diabetic foot ulcers

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Single-Cell RNA Profiling of Human Skin Reveals Age-Related Loss of Dermal Sheath Cells and Their Contribution to a Juvenile Phenotype

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Towards Precision Dermatology: Emerging Role of Proteomic Analysis of the Skin

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Summary: Proteomic analysis of the skin using LC-MS/MS has advanced our understanding of skin structure and function on a molecular level. Studies on healthy skin and skin diseases have the potential to identify biomarkers for diagnosis, patient stratification, and drug development, ultimately enhancing clinical practice and patient outcomes.

DERMATOLOGY (2022)

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Article Allergy

Single-cell analysis reveals innate lymphoid cell lineage infidelity in atopic dermatitis

Natalia Alkon et al.

Summary: This study investigates the phenotypic and molecular features of cutaneous innate lymphoid cells (ILCs) to better understand the biological role of these cells. The findings demonstrate the flexibility of the skin immune system, with ILCs in diseased skin expressing genes characteristic of different immune types. This suggests that the skin immune system can adjust its function to adapt to the environment.

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Article Dermatology

Single-Cell RNA-Sequencing Reveals Lineage-Specific Regulatory Changes of Fibroblasts and Vascular Endothelial Cells in Keloids

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Single-Cell Analysis Reveals Major Histocompatibility Complex II-Expressing Keratinocytes in Pressure Ulcers with Worse Healing Outcomes

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Alice Wang et al.

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Article Allergy

Single-cell RNA sequencing of psoriatic skin identifies pathogenic Tc17 cell subsets and reveals distinctions between CD8+ T cells in autoimmunity and cancer

Jared Liu et al.

Summary: This study utilized single-cell RNA sequencing to compare the transcriptomic heterogeneity of CD8(+) T cells in psoriatic and healthy skin, identifying several inflammatory subsets enriched in psoriatic skin and two Tc17 cell subsets associated with disease severity. Despite high expression of coinhibitory receptors, the psoriatic Tc17 cells exhibited upregulated cytokine, cytolytic, and metabolic activity, distinguishing them from an exhaustion program observed in melanoma-infiltrating CD8(+) T cells.

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Developmental cell programs are co-opted in inflammatory skin disease

Gary Reynolds et al.

Summary: The skin establishes a complex cellular network early in embryonic development to provide biophysical and immunological protection. The study found an enrichment of innate immune cells in skin during the first trimester, as well as clonal expansion of disease-associated lymphocytes in atopic dermatitis and psoriasis. Additionally, a reemergence of prenatal vascular endothelial cell and macrophage cellular programs was observed in atopic dermatitis and psoriasis lesional skin.

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Human cutaneous neurofibroma matrisome revealed by single-cell RNA sequencing

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Persistence of mature dendritic cells, TH2A, and Tc2 cells characterize clinically resolved atopic dermatitis under IL-4Rα blockade

Christine Bangert et al.

Summary: Therapeutic options for autoimmune diseases typically involve immunosuppressive agents, but sustained clinical benefit is rare. A study on atopic dermatitis patients treated with dupilumab found decreases in skin immune cell counts and normalization of transcriptomic dysregulation. However, specific immune cell populations persisted after clinical remission, indicating a persisting disease memory.

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Article Cell Biology

A Single-Cell Transcriptomic Atlas of Human Skin Aging

Zhiran Zou et al.

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Single-cell RNA sequencing reveals markers of disease progression in primary cutaneous T-cell lymphoma

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αβγ8 T cells play a vital role in fetal human skin development and immunity

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Summary: Single-cell analyses identified a naive T cell population expressing specific T cell receptors enriched in fetal skin and intestine. These cells may contribute to early skin development and fetal immune defense, showing fundamental differences in immune surveillance between fetal and adult human skin.

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Integrated spatial multiomics reveals fibroblast fate during tissue repair

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γδ T Cells in Merkel Cell Carcinomas Have a Proinflammatory Profile Prognostic of Patient Survival

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Spontaneously Resolved Atopic Dermatitis Shows Melanocyte and Immune Cell Activation Distinct From Healthy Control Skin

Katharina Rindler et al.

Summary: The study found that the overall cell composition and proteomic profiles of spontaneously healed atopic dermatitis (AD) patients were comparable to healthy controls, without the upregulation of typical AD activity markers. Melanocytes and conventional T-cells in spontaneously healed AD skin may play a role in providing a specific regulatory environment.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Genetics & Heredity

Direct Comparative Analyses of 10X Genomics Chromium and Smart-seq2

Xiliang Wang et al.

Summary: This study systematically evaluated the features and limitations of two frequently used single-cell RNA sequencing platforms, 10X Genomics Chromium and Smart-seq2, by comparing their data generated from the same CD45(-) cell samples. Smart-seq2 detected more genes in a cell, especially low abundance and alternatively spliced transcripts, while 10X-based data showed more severe dropout problems but could detect rare cell types. The study provides insights into the characteristics of these technologies and their applications in single-cell transcriptomics.

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Review Genetics & Heredity

Profiling Chromatin Accessibility at Single-cell Resolution

Sarthak Sinha et al.

Summary: The review outlines the molecular methods and bioinformatic tools for capturing cell-to-cell chromatin variation using scATAC-seq in a scalable fashion. It also covers joint profiling of chromatin with transcriptome/proteome measurements, computational strategies for multi-omic integration, and predictive bioinformatic tools for inferring chromatin accessibility from single-cell transcriptomic datasets. Methodological refinements that increase power for cell discovery and integrate measurements from multiple modalities will further expand understanding of gene regulation during homeostasis and disease.

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Article Allergy

Single-cell transcriptomics applied to emigrating cells from psoriasis elucidate pathogenic versus regulatory immune cell subsets

Jaehwan Kim et al.

Summary: This study utilized single-cell transcriptomics to analyze emigrating cells from the skin, revealing gene expression profiles of pathogenic and regulatory immune cell subsets in individuals with psoriasis. The findings also highlighted differences in key signaling pathways in psoriasis.

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Article Cell Biology

Single cell transcriptional zonation of human psoriasis skin identifies an alternative immunoregulatory axis conducted by skin resident cells

Yuge Gao et al.

Summary: Psoriasis, the most common skin disease in adults, involves a complex interplay between infiltrating immune cells and local resident skin cells. Studies have shown a potential feedback signaling loop from skin cells to immune cells, with an evolutionally conserved cellular response. Differential gene expression related to psoriasis susceptibility loci and cell types play a crucial role in the development of psoriasis.

CELL DEATH & DISEASE (2021)

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Review Medicine, General & Internal

Single-cell transcriptomics: a novel precision medicine technique in nephrology

Jisoo Kim et al.

Summary: Single-cell analysis techniques can clarify key issues in kidney biology and disease pathogenesis, identify disease-related biomarkers and pathways, stratify patients, and determine appropriate treatment methods.

KOREAN JOURNAL OF INTERNAL MEDICINE (2021)

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Single-cell transcriptome analysis identifies skin-specific T-cell responses in systemic sclerosis

Alyxzandria M. Gaydosik et al.

Summary: Through single-cell transcriptome analysis, different subsets of T cells in healthy and SSc skin were identified, each associated with distinct signaling pathways. A unique subset of recirculating CXCL13(+) T cells in SSc skin was discovered, expressing a T helper follicular-like gene expression signature and potentially promoting B-cell responses in the inflamed skin of patients.

ANNALS OF THE RHEUMATIC DISEASES (2021)

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Single-cell RNA sequencing profiling in a patient with discordant primary cutaneous B-cell and T-cell lymphoma reveals micromilieu-driven immune skewing

C. Jonak et al.

Summary: This study utilized single-cell RNA sequencing and T-cell and B-cell receptor sequencing to molecularly characterize a complex type of primary cutaneous lymphoma. The results revealed a patient with concurrent mycosis fungoides (MF) and primary cutaneous follicle centre lymphoma (PCFCL), with distinct immune phenotypes in the two types of lymphoma lesions. The data not only demonstrate the diagnostic potential of single-cell RNA sequencing, but also provide insights into the unique tissue microenvironment shaped by specific clonal populations in clinically distinct types of lymphoma skin lesions.

BRITISH JOURNAL OF DERMATOLOGY (2021)

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Distinct human Langerhans cell subsets orchestrate reciprocal functions and require different developmental regulation

Xiaochun Liu et al.

Summary: This study identified two steady-state (LC1 and LC2) and two activated LC subsets in human skin epidermis and LCs derived from CD34(+) hemopoietic stem cells. LC1 were characterized as classical LCs mainly related to innate immunity and antigen processing, while LC2 were similar to monocytes or myeloid dendritic cells, involving in immune responses and leukocyte activation. These distinct human LC subsets require different developmental regulation and orchestrate reciprocal functions.

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Single-cell omics: Overview, analysis, and application in biomedical science

Catarina M. Stein et al.

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Article Immunology

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

Satoshi Nakamizo et al.

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Rachel L. Belote et al.

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NATURE IMMUNOLOGY (2021)

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Paul Datlinger et al.

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scRNA-seq of human vitiligo reveals complex networks of subclinical immune activation and a role for CCR5 in Treg function

Kyle J. Gellatly et al.

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RNA BIOLOGY (2017)

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Comparative Analysis of Single-Cell RNA Sequencing Methods

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MOLECULAR CELL (2017)

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NATURE (2017)

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Simultaneous epitope and transcriptome measurement in single cells

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Seq-Well: portable, low-cost RNA sequencing of single cells at high throughput

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NATURE METHODS (2017)

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Single cell RNA sequencing to dissect the molecular heterogeneity in lupus nephritis

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JCI INSIGHT (2017)

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Review Dermatology

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EXPERIMENTAL DERMATOLOGY (2016)

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Single-cell triple omics sequencing reveals genetic, epigenetic, and transcriptomic heterogeneity in hepatocellular carcinomas

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Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq

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SCIENCE (2016)

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Review Cell Biology

Single Cell Isolation and Analysis

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FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2016)

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Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets

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CELL (2015)

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G&T-seq: parallel sequencing of single-cell genomes and transcriptomes

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NATURE METHODS (2015)

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Review Dermatology

High throughput investigative dermatology in 2012 and beyond: A new era beckons

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AUSTRALASIAN JOURNAL OF DERMATOLOGY (2013)

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Smart-seq2 for sensitive full-length transcriptome profiling in single cells

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NATURE METHODS (2013)

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mRNA-Seq whole-transcriptome analysis of a single cell

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