Dataset Information

Proteome dataset of cultured human bone marrow derived stromal (stem) cells, adipocytes and osteoblasts

ABSTRACT: Mesenchymal stromal stem cells (MSCs) gain increasing focus in the field of regenerative medicine due to their differentiational abilities into chondrocytes, adipocytes and osteoblastic cells. However, it is apparent that the transformation processes are extremely complex, cause cellular heterogeneity and need further insights into functional annotation. The aim of the study was to characterize differences between MSCs and cells after adipogenic or osteoblastic differentiation at the proteome level. For this, we analysed the proteome of isolated and cultured MSCs and after differentiation into adipogenic and osteoblastic cell lineages using electrospray ionization tandem mass spectrometry in data-independent acquisition mode. Protein inference and quantification was performed using deep neural networks in library free mode. By jointly using strict differential expression analysis and machine learning algorithms, two cell type specific marker protein panels for the osteoblastic and the adipocytic lineage were identified which allow for distinguishment of the three cell types.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Thorben Sauer

LAB HEAD: Timo Gemoll

PROVIDER: PXD029900 | Pride | 2022-03-25

REPOSITORIES: Pride

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Publications

Protein Expression of AEBP1, MCM4, and FABP4 Differentiate Osteogenic, Adipogenic, and Mesenchymal Stromal Stem Cells.

Sauer Thorben T Facchinetti Giulia G Kohl Michael M Kowal Justyna M JM Rozanova Svitlana S Horn Julia J Schmal Hagen H Kwee Ivo I Schulz Arndt-Peter AP Hartwig Sonja S Kassem Moustapha M Habermann Jens K JK Gemoll Timo T

International journal of molecular sciences 20220225 5

Mesenchymal stem cells (MSCs) gain an increasing focus in the field of regenerative medicine due to their differentiation abilities into chondrocytes, adipocytes, and osteoblastic cells. However, it is apparent that the transformation processes are extremely complex and cause cellular heterogeneity. The study aimed to characterize differences between MSCs and cells after adipogenic (AD) or osteoblastic (OB) differentiation at the proteome level. Comparative proteomic profiling was performed usin ...[more]

PMID: 35269711

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Project description:Purpose: Chemotherapy is pivotal in the multimodal treatment of pancreatic cancer patients. In recent years, technical advances have developed experimental methods that unveiled a high degree of inter- and intratumoral heterogeneity in pancreatic cancer. We hypothesized that intratumoral heterogeneity (ITH) impacts response to gemcitabine treatment and demands specific targeting of resistant subclones. Experimental Design: We addressed the effect of ITH on response to gemcitabine treatment using single cell-derived cell lines (SCDCL) from the classical-like cell line BxPC3 and the basal-like cell line Panc-1 which were analyzed by mRNA-seq and mass spectrometry. Results: Individual SCDCLs of the parental tumor cell populations of BxPC3 and Panc-1 showed considerable heterogeneity in response to gemcitabine. Unsupervised principal component analysis (PCA) including the 1,000 most variably expressed genes showed a clustering of the SCDCLs according to their respective sensitivity to gemcitabine treatment for BxPC3, while this clustering was less clear for Panc-1. In BxPC3 SCDCLs, enriched signaling pathways EMT, TNF signaling via NfKB, and IL2STAT5 signaling correlated with more resistant behavior to gemcitabine. In Panc-1 SCDCLs MYC targets V1 and V2 as well as E2F targets were associated with stronger resistance to gemcitabine. Feature extraction of proteomes again identified less proteins whose expression was associated with the response of individual SCDCLs in Panc-1 compared to BxPC3. Based on molecular profiles, we could show that the gemcitabine-resistant SCDCLs of both BxPC3 and Panc-1 are more sensitive to the BET inhibitor JQ1 compared to the respective gemcitabine-sensitive SCDCLs. Conclusions: Our model system of SCDCLs identified gemcitabine-resistant subclones within a parental tumor population and provides evidence for the critical role of ITH for treatment response in pancreatic cancer. Through molecular profiling, we identified specific signaling pathways and protein signatures that might help to explain the differential response to treatment among clones. We exploited these molecular differences for an improved and more targeted therapy of resistant subclones of a heterogeneous tumor.

Dataset Information

Proteome dataset of cultured human bone marrow derived stromal (stem) cells, adipocytes and osteoblasts

Publications

Protein Expression of AEBP1, MCM4, and FABP4 Differentiate Osteogenic, Adipogenic, and Mesenchymal Stromal Stem Cells.

Similar Datasets

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