Landscape of transcription and expression regulated by DNA methylation related to age of donor and cell passage in adipose-derived mesenchymal stem cells

Lu, Guan-Ming; Rong, Yong-Xian; Liang, Zheng; Hunag, Dong-Lin; Ma, Yuju; Luo, Zhizhai; Wu, Fengyao; Liu, Xinheng; Liu, Yu; Mo, Steven; Qi, Zhongquan; Li, Hong-Mian

doi:10.18632/aging.103809

Cited by 10 publications

(11 citation statements)

References 45 publications

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“…The volcano plots were generated by ggplot2 in R tools . The R package “clusterprofile” was applied for the gene ontology (GO) . The principal component analysis (PCA) was performed using the R package “factoextra” …”

Section: Methodsmentioning

confidence: 99%

Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer

Chang,

Chen,

Yin

et al. 2024

J. Proteome Res.

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Bladder cancer (BCa) is the predominant malignancy of the urinary system. Herein, a comprehensive urine proteomic feature was initially established for the noninvasive diagnosis and recurrence monitoring of bladder cancer. 279 cases (63 primary BCa, 87 nontumor controls (NT), 73 relapsed BCa (BCR), and 56 nonrelapsed BCa (BCNR)) were collected to screen urinary protein biomarkers. 4761 and 3668 proteins were qualified and quantified by DDA and sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis in two discovery sets, respectively. Upregulated proteins were validated by multiple reaction monitoring (MRM) in two independent combined sets. Using the multi-support vector machine-recursive feature elimination (mSVM-RFE) algorithm, a model comprising 13 proteins exhibited good performance between BCa and NT with an AUC of 0.821 (95% CI: 0.675−0.967), 90.9% sensitivity (95% CI: 72.7−100%), and 73.3% specificity (95% CI: 53.3− 93.3%) in the diagnosis test set. Meanwhile, an 11-marker classifier significantly distinguished BCR from BCNR with 75.0% sensitivity (95% CI: 50.0−100%), 81.8% specificity (95% CI: 54.5−100%), and an AUC of 0.784 (95% CI: 0.609−0.959) in the test cohort for relapse surveillance. Notably, six proteins (SPR, AK1, CD2AP, ADGRF1, GMPS, and C8A) of 24 markers were newly reported. This paper reveals novel urinary protein biomarkers for BCa and offers new theoretical insights into the pathogenesis of bladder cancer (data identifier PXD044896).

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Section: Methodsmentioning

confidence: 99%

Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer

Chang,

Chen,

Yin

et al. 2024

J. Proteome Res.

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“…For the microarray performed using this dataset, we acquired the normalized matrix data directly through download. For the TCGA dataset, RNA sequencing data of gene expression were acquired from the GDC via the R Package-Age TCGA biolinks ( 29 ), which was developed particularly for comprehensive assays of GDC data. Somatic mutation information was obtained from the TCGA database.…”

Section: Methodsmentioning

confidence: 99%

m6A Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Acute Myeloid Leukemia

Gao

et al. 2021

Front. Immunol.

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Recent studies have demonstrated epigenetic regulation of immune responses. Nevertheless, the underlying effect of RNA N6-methyladenosine (m6A) modifications on tumor microenvironment cell infiltration remains elusive. In this study, we thoroughly assessed m6A modification patterns of 255 myeloid leukemia specimens based on 23 m6A regulators. Consensus clustering of the 23 m6A regulators was performed to determine three distinct m6A modification patterns that were remarkably consistent with three immunophenotypes of tumors: immunorejection, immune activation, and immune inertness. Further evaluation and prognostic analysis of the m6A modification patterns of individual tumors revealed that low m6A score was characterized by increased mutational burden, immune activation, and survival rates, whereas high m6A score was characterized by poorer survival rates and the absence of effective immune infiltration. In addition, this study investigated the association between m6A regulators and antitumor immune responses and discovered higher expression of the immune regulators PD-L1, PD-L2, MRP1, and MRP2 in low m6A scores. Generally, the expression pattern of m6A regulators was remarkably associated with prognostic results and antitumor immune responses in acute myeloid leukemia and may be an underlying target and biological marker for immune therapies.

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“…7 Consequently, MSCs applied in a clinical setting are likely to be isolated from older patients, highlighting the importance of understanding the effect of age on MSC potency. Donor age and sex affect multiple MSC functions including proliferation and differentiation, [8][9][10][11][12][13][14][15] immunomodulation, 16 gene expression, 14,[17][18][19] DNA methylation 20,21 and energy metabolism. 20 However, the effect of donor characteristics on protein secretion in MSCs is less well explored.…”

Section: Introductionmentioning

confidence: 99%

“…Donor age and sex affect multiple MSC functions including proliferation and differentiation, 8–15 immunomodulation, 16 gene expression, 14,17–19 DNA methylation 20,21 and energy metabolism. 20 However, the effect of donor characteristics on protein secretion in MSCs is less well explored.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stromal Cell secretome is affected by tissue source, donor age and sex

Turło¹,

Hammond²,

Ramsbottom³

et al. 2023

Preprint

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Variation in Mesenchymal Stromal Cell (MSC) function depending on their origin is problematic, as it may confound clinical outcomes of MSC therapy. Current evidence suggests that the therapeutic benefits of MSCs is primarily attributed to secretion of various biologically active factors (secretome). However, the effect of donor characteristics on the MSC secretome composition remains largely unknown. Here, we examined the influence of donor age, sex and tissue source, on the protein profile of the equine MSC secretome. Initially, we used dynamic metabolic labelling with stable isotopes combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify secreted proteins in MSC conditioned media (CM). Seventy proteins were classified as classically-secreted based on the rate of isotope label incorporation into newly synthesised proteins released into the extracellular space. Next, we analysed CM of bone marrow- (n = 14) and adipose-derived MSCs (n = 16) with label-free LC-MS/MS proteomics. Clustering analysis of 314 proteins detected across all samples identified tissue source as the main factor driving variability in MSC CM proteomes. Linear modelling applied to the subset of 70 secreted proteins identified tissue-related difference in the abundance of 23 proteins. There was an age-related decrease in the abundance of two proteins (CTHRC1, LOX), which has been validated with western blot and enzymatic activity assay. There was limited evidence of sex-related differences in protein abundance. In conclusion, this study provides evidence that tissue source and donor age contribute to heterogeneity in the protein composition of MSC secretomes which may influence the effects of MSC-based cell therapy.

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Landscape of transcription and expression regulated by DNA methylation related to age of donor and cell passage in adipose-derived mesenchymal stem cells

Cited by 10 publications

References 45 publications

Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer

Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer

m6A Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Acute Myeloid Leukemia

Mesenchymal Stromal Cell secretome is affected by tissue source, donor age and sex

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