Dataset Information

Application of Proteomic Workflows for the Identification of Biomarkers for Retrospective Verification of Sulfur Mustard Intoxication

ABSTRACT: The family of sulfur mustards as potent alkylating agents have been used as chemical warfare agents for over a century. The retrospective verification of exposure and, hence, the confirmation of alleged use of this agent remains a challenging task with high demand for resources in the identification, preparation, and analysis of potential specific biomarkers. We herein report a facile and high-throughput methodology demonstrated for biomedical samples using known proteomic workflows and implementing statistical models.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

SUBMITTER: Gianin Thomann

LAB HEAD: Maximilian Brackmann

PROVIDER: PXD068389 | Pride | 2026-04-02

REPOSITORIES: Pride

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Source:

			Action	DRS
	5023_GT240617_a_1-1_Slot2-2_25min_AUR15_300nl_50deg_6-19-2024_17-10-42.d.zip	Other
	5024_GT240617_a_3-1_Slot2-10_25min_AUR15_300nl_50deg_6-19-2024_17-53-25.d.zip	Other
	5025_GT240617_a_3-UCS_Slot2-9_25min_AUR15_300nl_50deg_6-19-2024_18-35-10.d.zip	Other
	5026_GT240617_a_2-3_Slot2-8_25min_AUR15_300nl_50deg_6-19-2024_19-16-52.d.zip	Other
	5027_GT240617_a_QC1S_Slot2-13_25min_AUR15_300nl_50deg_6-19-2024_19-58-32.d.zip	Other

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Project description:Extracellular vesicles derived from induced pluripotent stem cells (iPSC EVs) have immunoregulatory potential with the ability to alter monocyte-derived macrophages. Macrophages function in the propagation and resolution of inflammation which is mediated by their phenotype. Macrophages are an ideal therapeutic target as modulating their phenotype towards an anti-inflammatory pro-resolving state may be beneficial in chronic inflammatory diseases such as atherosclerosis. Macrophages are naturally phagocytotic cells and readily take up iPSC EVs however the contents of iPSC EVs and their effects on macrophages are poorly understood. Here iPSC EVs were characterized and analysed by mass-spectrometry based proteomics and a targeted microRNA (miR) panel. Their immunomodulatory effects on macrophages were assessed and a monocyte transmigration assay was used to assess the chemotactic potency of the secretome from iPSC EV treated macrophages. Proteomic analysis on iPSC EVs identified Podocalyxin-like protein 1 (PODXL1), Insulin (INS) and Solute Carrier Family 2 (Facilitated Glucose Transporter), Member 3 (SLC2A3) as the most abundant proteins unique to the iPSC EVs when compared to control NT-2 EVs. Notably, thioredoxin and peroxiredoxin related proteins were detected. miR-302d-3p was the most abundant miR in these iPSC EVs. miR-25-3p, previously reported to alter the macrophage phenotype, was significantly increased in comparison to the control NT-2 EVs. iPSC EVs increased expression of the anti-inflammatory associated MRC1 and miR-21 in human primary macrophages and decreased monocyte chemoattractant protein1 (MCP-1). Mass spectrometry based proteomics revealed that treated macrophages had decreased levels of secretory proteins, some of which have chemotactic properties, these included Azurocidin 1 (AZU1), Growth Differentiation Factor 15 (GDF15), and Ribosomal Protein S19 (RPS19). There was a decrease in monocyte transmigration towards conditioned media from macrophages treated with iPSC EVs. Collectively this study provides insights into the protein content and miR cargo of iPSC EVs and highlights their capacity to inhibit chemotactic proteins in macrophages and upregulate MRC1.

Dataset Information

Application of Proteomic Workflows for the Identification of Biomarkers for Retrospective Verification of Sulfur Mustard Intoxication

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