Dataset Information

LgG4 lesion of EoE patient biopsy by AutoSTOMP

ABSTRACT: To test the ability of the Automated Spatially Targeted Optical Micro Proteomics (AutoSTOMP) protocol for clinical research. We collected from a patient diagnosed with active EoE (≥15 eosinophils/hpf), according to consensus guidelines, using standard endoscopy procedures, then we try to selectively obtain the proteome from the discrete lgG4+ lesions of the biopsy sections by AutoSTOMP, and try to link the lesion structure with its specially skewed constituents comparing to the rest of the tissue.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Esophagus

SUBMITTER: BOCHENG YIN

LAB HEAD: Sarah E. Ewald

PROVIDER: PXD026819 | Pride | 2021-08-10

REPOSITORIES: Pride

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Publications

Automated Spatially Targeted Optical Microproteomics Investigates Inflammatory Lesions <i>In Situ</i>.

Yin Bocheng B Caggiano Laura R LR Li Rung-Chi RC McGowan Emily E Holmes Jeffrey W JW Ewald Sarah E SE

Journal of proteome research 20210826 9

Tissue microenvironment properties like blood flow, extracellular matrix, or proximity to immune-infiltrate are important regulators of cell biology. However, methods to study regional protein expression in the native tissue environment are limited. To address this need, we developed a novel approach to visualize, purify, and measure proteins <i>in situ</i> using automated spatially targeted optical microproteomics (AutoSTOMP). Here, we report custom codes to specify regions of heterogeneity in ...[more]

PMID: 34436902

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Project description:Ineffective hematopoiesis is a hallmark of myelodysplastic syndromes (MDS). Hematopoietic alterations in MDS patients strictly correlate with microenvironment dysfunctions, eventually affecting also the mesenchymal stromal cells (MSCs) compartment. Stromal cells are indeed epigenetically reprogrammed to cooperate with leukemic cells and propagate the disease as "tumor unit"; therefore, changes on MSCs epigenetic profile might contribute to the hematopoietic perturbations typical of MDS. Here, we unveil that the histone variant macroH2A1 (mH2A1) regulates the crosstalk between epigenetics and inflammation in MDS-MSCs, potentially affecting their hematopoietic support ability. We show that the mH2A1 splicing isoform mH2A1.1 accumulates in MDS-MSCs, correlating with the expression of the Toll-like receptor 4 (TLR4), an important pro-tumor activator of MSC phenotype associated to a pro-inflammatory behavior. MH2A1.1-TLR4 axis was further investigated in HS-5 stromal cells after ectopic mH2A1.1 overexpression (mH2A1.1-OE). Proteomic data confirmed the activation of a pro-inflammatory signature associated to TLR4 and nuclear factor kappa B (NFkB) activation. Moreover, mH2A1.1-OE proteomic profile identified several upregulated proteins associated to DNA and histones hypermethylation, including S-adenosylhomocysteine hydrolase, a strong inhibitor of DNA methyltransferase and of the methyl donor S-adenosyl-methionine (SAM). HPLC analysis confirmed higher SAM/SAH ratio along with a metabolic reprogramming. Interestingly, an increased LDHA nuclear localization was detected both in mH2A1.1-OE cells and MDS-MSCs, probably depending on MSC inflammatory phenotype. Finally, coculturing healthy mH2A1-OE MSCs with CD34+ cells, we found a significant reduction in the number of CD34+ cells, which was reflected in a decreased number of colony forming units (CFU -Cs). These results suggest a key role of mH2A1.1 in driving the crosstalk between epigenetic signaling, inflammation and cell metabolism networks in MDS-MSCs.

Dataset Information

LgG4 lesion of EoE patient biopsy by AutoSTOMP

Publications

Automated Spatially Targeted Optical Microproteomics Investigates Inflammatory Lesions <i>In Situ</i>.

Similar Datasets

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