Project description:The mast cell-specific metalloprotease CPA3 has been given important roles in lung tissue homeostasis and disease pathogenesis. However, the dynamics and spatial distribution of mast cells CPA3 expression in lung diseases remains unknown. Methods: Using a histology-based approach for spatial and quantitative simultaneous decoding of mRNA and protein expression at a single cell level, this study investigates the dynamics of CPA3 expression across mast cells residing in lungs from healthy controls and patients with severe chronic obstructive pulmonary disease (COPD) or idiopathic lung fibrosis (IPF). Results: Mast cells in COPD lungs had increased CPA3 mRNA (bronchioles p<0.001, pulmonary vessels p< 0.01, alveolar parenchyma p< 0.01) compared to controls, while granule stored CPA3 protein was unaltered. IPF lungs had a significant upregulation of both CPA3 mRNA (p<0.001) and protein (p<0.05) in the fibrotic alveolar tissue. IPF was also characterized by highest density of distal lung mast cells. As an indication of disease relevant increased CPA3 turnover, spatial expression maps revealed altered mast cell mRNA/protein quotients in lung areas subjected to disease-relevant histopathological alterations. Single cell RNA sequencing of bronchial mast cells confirmed CPA3 as a top expressed gene with potential links to both inflammatory and protective markers. Conclusion: This study shows that lung tissue mast cell populations in COPD and IPF-affected lungs have spatially complex and markedly up-regulated CPA3 expression profiles that correlates with sites of structural pathologies. Given the proposed roles of CPA3 in tissue homeostasis, remodeling and inflammation, these alterations are likely to have clinical consequences.

2022-07-28 | GSE201772 | GEO

Expression data from mouse mast cell progenitors, mature mast cells and innate lymphoid cells of type 2

Project description:Mast cells originate from the bone marrow and develop into c-kit+ FcεRI+ cells. As both mast cell progenitors and mature mast cells express these cell surface markers, ways validated to distinguish between the two maturation forms with flow cytometry have been lacking. We identified and sorted two distinct populations of mast cells from mouse peritoneum. Gene expression microarray analyses were used to confirm the maturation statuses of the mast cell populations.

2015-03-07 | GSE63507 | GEO

Single-cell RNA sequencing of human peripheral blood progenitors captures early mast cell differentiation

Project description:Activation of mast cells through FcεRI can result in allergic responses. The identity of mast cells progenitors is controversial, in particular whether these cells express FcεRI. Here, we performed single-cell RNA sequencing of human peripheral blood progenitors to study the appearance of FcεRI during hematopoietic progenitor differentiation.

2022-05-03 | GSE184351 | GEO

Human connective tissue mast cell proteome

Project description:Mast cells are hematopoietic cells that reside preferentially in tissues exposed to internal and external environments. Mast cells sense immunological, inflammatory and environmental stimuli, and can be activated to release granules and generate inflammatory mediators. Mast cell-derived products confer protection against snake venoms and some parasite infections. Aberrant activation of mast cells is a major contributor to human pathology, including allergy, asthma and adverse drug reactions. Their strict tissue location has largely impeded the isolation of large numbers of primary mast cell for further analysis. To better understand the biology of mast cells, we analyzed the proteome of primary human and mouse mast cells by quantitative mass spectrometry. We identified a mast cell-specific protein signature that was conserved from mouse to man. Compared to a comprehensive set of other immune cell lineages, proteome analysis identified a unique and distant mast cell cluster. The mast cell signature included proteins governing granule biosynthesis and secretion, as well as proteoglycan- and neurotransmitter metabolism. Proteome conservation across species suggests evolutionary maintenance of mast cell functions.

2020-02-12 | PXD014978 | Pride

Dynamically Upregulated Mast Cell CPA3 Patterns in lung disease

Project description:Dynamically Upregulated Mast Cell CPA3 Patterns in lung disease

| PRJNA832973 | ENA

Single-cell transcriptional profiling of late mast cell differentiation in mouse

Project description:Single-cell RNA sequencing of Lin- c-Kit+ FcεRI+ cells from mouse peritoneum captured the late mast cell differentiation

2020-10-20 | GSE128003 | GEO

FACS sorted podocytes, mesangial cells

Project description:FACS sorted glomerular kidney cells from a single mouse were subjected to proteomics.

2022-10-13 | PXD016237 | Pride