Myofibroblast transcriptome indicates SFRP2+ fibroblast progenitors in systemic sclerosis skin

Tabib, Tracy; Huang, Meng; Morse, Christina; Papazoglou, Anna; Behera, Rithika; Jia, Minxue; Bulik, Melissa; Monier, Daisy; Benos, Panayiotis V.; Chen, W.; Domsic, Robyn T.; Lafyatis, Robert

doi:10.1101/2021.04.30.442148

Cited by 17 publications

(35 citation statements)

References 86 publications

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“…A cluster of preadipocytes (mixed with ASC) express metallothionein genes, and a separate cluster express ISG15 and other IFN-related genes ( Figure 4A ). Finally, we identified several fibroblastic cell populations similar to those recently described in the dermis (Tabib et al, 2021). One population expressing SFRP2, DPP4, and PCOLCE2 is analogous to the PCOLCE+ fibroblast.…”

Section: Resultssupporting

confidence: 66%

“…Comparing non-diabetic, prediabetic and diabetic PWH, myeloid (median percent: 34.1%, 19.3%, 23.7%, respectively; p = 0.23) and lymphoid (median percent: 24.7%, 8.8%, 15.1%, respectively; p = 0.17) proportions were not significantly different (Figure 1E). Age and sex can influence adipocyte function and immune cell populations (Caso et al, 2013;Chang et al, 2018;Huang et al, 2021;Vasanthakumar et al, 2020), but we found no significant differences in cell proportions after stratifying by these factors. Taken together, these data represent the largest single-cell genomic, and first proteogenomic, comprehensive atlas of scWAT, as well as the first characterization of scWAT in persons with diabetes and HIV infection.…”

Section: Heterogeneity Of Cell Populations By Disease Statecontrasting

confidence: 64%

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White Adipose Tissue Compositional and Transcriptional Patterns with Progressive Glucose Intolerance in Persons with HIV

Bailin

Kropski

Gangula

et al. 2022

Preprint

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Subcutaneous white adipose tissue (scWAT) is a critical regulator of systemic metabolic homeostasis. HIV infection is accompanied by alterations in scWAT immune cells, which may contribute to the increased risk for cardiometabolic diseases in persons with HIV (PWH) and serve as a model to investigate cellular relationships. We generated the largest molecular atlas of scWAT in humans to date from 91 individuals using paired single-cell transcriptomic and proteogenomics to determine the scWAT immune profile in non-diabetic, pre-diabetic, and diabetic PWH, and HIV-negative diabetic persons. We identified a substantial increase in lipid- associated macrophages (LAMs) with glucose intolerance, and, in PWH only, CD4+ and CD8+ T effector memory cells were correlated with LAM proportion. Finally, we resolved adipogenic and fibrogenic cells at high resolution and found a strong association between LAMs and myofibroblasts. These results provide a high-resolution, multi-platform characterization of changes in scWAT composition that occur with metabolic disease and HIV.

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Section: Resultssupporting

confidence: 66%

Section: Heterogeneity Of Cell Populations By Disease Statecontrasting

confidence: 64%

White Adipose Tissue Compositional and Transcriptional Patterns with Progressive Glucose Intolerance in Persons with HIV

Bailin

Kropski

Gangula

et al. 2022

Preprint

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show abstract

“…Using single‐cell RNA‐seq analysis, we examined gene expression of all enzymatically digested skin cells obtained from 12 patients with dcSSc and 10 healthy control subjects. All subjects have been included in another analysis of fibroblasts in fibrotic skin (19). Patients with dcSSc and control subjects were balanced across sex and age (Supplementary Table 1, available on the Arthritis & Rheumatology website at https://doi.org/10.1002/art.41813/abstract).…”

Section: Resultsmentioning

confidence: 99%

Expansion of Fcγ Receptor IIIa–Positive Macrophages, Ficolin 1–Positive Monocyte‐Derived Dendritic Cells, and Plasmacytoid Dendritic Cells Associated With Severe Skin Disease in Systemic Sclerosis

Xue

Tabib

Morse

et al. 2022

Arthritis & Rheumatology

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Objective In this study, we sought a comprehensive understanding of myeloid cell types driving fibrosis in diffuse cutaneous systemic sclerosis (dcSSc) skin. Methods We analyzed the transcriptomes of 2,465 myeloid cells from skin biopsy specimens from 12 dcSSc patients and 10 healthy control subjects using single‐cell RNA sequencing. Monocyte‐derived dendritic cells (mo‐DCs) were assessed using immunohistochemical staining and immunofluorescence analyses targeting ficolin‐1 (FCN‐1). Results A t‐distributed stochastic neighbor embedding analysis of single‐cell transcriptome data revealed 12 myeloid cell clusters, 9 of which paralleled previously described healthy control macrophage/DC clusters, and 3 of which were dcSSc‐specific myeloid cell clusters. One SSc‐associated macrophage cluster, highly expressing Fcγ receptor IIIA, was suggested on pseudotime analysis to be derived from normal CCR1+ and MARCO+ macrophages. A second SSc‐associated myeloid population highly expressed monocyte markers FCN‐1, epiregulin, S100A8, and S100A9, but was closely related to type 2 conventional DCs on pseudotime analysis and identified as mo‐DCs. Mo‐DCs were associated with more severe skin disease. Proliferating macrophages and plasmacytoid DCs were detected almost exclusively in dcSSc skin, the latter clustering with B cells and apparently derived from lymphoid progenitors. Conclusion Transcriptional signatures in these and other myeloid populations indicate innate immune system activation, possibly through Toll‐like receptors and highly up‐regulated chemokines. However, the appearance and activation of myeloid cells varies between patients, indicating potential differences in the underlying pathogenesis and/or temporal disease activity in dcSSc.

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“…A recent study discovered that DPP4expressing fibroblasts are responsible for collagen deposition in dermal scars and inhibition of DPP4 reduced scar formation in a mouse model of wound healing (16). The following studies demonstrated that SFRP2/DPP4 fibroblast subpopulation is the progenitor of fibrogenic fibroblasts in SSc skin (136) and DPP4 activated NF-kB and SMAD signaling through PAR2, leading to the activation of dermal fibroblasts (92).…”

Section: Dpp4 In Systemic Sclerosismentioning

confidence: 87%

Emerging Role of Dipeptidyl Peptidase-4 in Autoimmune Disease

et al. 2022

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Dipeptidyl-peptidase IV (DPP4), originally identified as an aminopeptidase in 1960s, is an ubiquitously expressed protease presented as either a membrane-bound or soluble form. DPP4 cleaves dipeptide off from the N-terminal of its substrates, altering the bioactivity of its substrates. Subsequent studies reveal that DPP4 is also involved in various cellular processes by directly binding to a number of ligands, including adenosine deaminase, CD45, fibronectin, plasminogen, and caveolin-1. In recent years, many novel functions of DPP4, such as promoting fibrosis and mediating virus entry, have been discovered. Due to its implication in fibrotic response and immunoregulation, increasing studies are focusing on the potential role of DPP4 in inflammatory disorders. As a moonlighting protein, DPP4 possesses multiple functions in different types of cells, including both enzymatic and non-enzymatic functions. However, most of the review articles on the role of DPP4 in autoimmune disease were focused on the association between DPP4 enzymatic inhibitors and the risk of autoimmune disease. An updated comprehensive summary of DPP4’s immunoregulatory actions including both enzymatic dependent and independent functions is needed. In this article, we will review the recent advances of DPP4 in immune regulation and autoimmune rheumatic disease.

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Myofibroblast transcriptome indicates SFRP2+ fibroblast progenitors in systemic sclerosis skin

Cited by 17 publications

References 86 publications

White Adipose Tissue Compositional and Transcriptional Patterns with Progressive Glucose Intolerance in Persons with HIV

White Adipose Tissue Compositional and Transcriptional Patterns with Progressive Glucose Intolerance in Persons with HIV

Expansion of Fcγ Receptor IIIa–Positive Macrophages, Ficolin 1–Positive Monocyte‐Derived Dendritic Cells, and Plasmacytoid Dendritic Cells Associated With Severe Skin Disease in Systemic Sclerosis

Emerging Role of Dipeptidyl Peptidase-4 in Autoimmune Disease

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