Alterations in genetic and protein content of swine adipose tissue-derived mesenchymal stem cells in the metabolic syndrome

Aditya S. Pawar, Alfonso Eirin, James D. Krier, John R. Woollard, Xiang Yang Zhu, Amir Lerman, Andre J van Wijnen, Lilach O Lerman

Research output: Contribution to journalArticle

Abstract

Introduction: Mesenchymal stem cells (MSCs) possess endogenous reparative properties and may serve as an exogenous therapeutic intervention in patients with chronic kidney disease. Cardiovascular risk factors clustering in the metabolic syndrome (MetS) might adversely affect cellular properties. To test the hypothesis that Mets interferes with MSC characteristics, we performed comprehensive comparison of the mRNA, microRNA, and protein content of MSCs isolated from Lean and MetS pigs. Methods: Domestic pigs were fed a 16-week Lean or MetS diet (n = 4 each). Expression profiles of co-existing microRNAs, mRNAs, and proteins were obtained by high-throughput sequencing and liquid chromatography-mass spectrometry. TargetScan and ComiR were used to predict target genes of differentially expressed microRNAs, and DAVID 6.7 for functional annotation analysis to rank primary gene ontology categories for the microRNA target genes, mRNAs, and proteins. Results: Differential expression analysis revealed 12 microRNAs upregulated in MetS-MSCs compared to Lean-MSCs (fold change>1.4, p <.05), which target 7728 genes, whereas 33 mRNAs and 78 proteins were downregulated (fold change<0.7, p <.05). Integrated analysis showed that targets of those microRNAs upregulated in MetS-MSCs overlap with at least half of mRNAs and proteins dysregulated in those cells. Functional analysis of overlapping mRNAs and proteins suggest that they are primarily involved in mitochondria, inflammation and transcription. MetS-MSCs also exhibited increased nuclear translocation of nuclear factor kappa-B, associated with increased SA-β-Galactosidase and decreased cytochrome-c oxidase-IV activity. Conclusion: MetS alters the transcriptome and proteome of swine adipose tissue-derived MSCs particularly genes involved in mitochondria, inflammation and transcription regulation. These alterations might limit the reparative function of endogenous MSC and their use as an exogenous regenerative therapy.

Original languageEnglish (US)
Article number101423
JournalStem Cell Research
Volume37
DOIs
StatePublished - May 1 2019

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Mesenchymal Stromal Cells
Adipose Tissue
Swine
MicroRNAs
Messenger RNA
Proteins
Mitochondria
Galactosidases
Genes
Inflammation
Sus scrofa
Gene Ontology
NF-kappa B
Electron Transport Complex IV
Proteome
Chronic Renal Insufficiency
Transcriptome
Liquid Chromatography
Cluster Analysis
Mass Spectrometry

Keywords

  • Mesenchymal stem cells
  • microRNA
  • Proteomics
  • Senescence
  • Sequencing

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

Alterations in genetic and protein content of swine adipose tissue-derived mesenchymal stem cells in the metabolic syndrome. / Pawar, Aditya S.; Eirin, Alfonso; Krier, James D.; Woollard, John R.; Zhu, Xiang Yang; Lerman, Amir; van Wijnen, Andre J; Lerman, Lilach O.

In: Stem Cell Research, Vol. 37, 101423, 01.05.2019.

Research output: Contribution to journalArticle

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abstract = "Introduction: Mesenchymal stem cells (MSCs) possess endogenous reparative properties and may serve as an exogenous therapeutic intervention in patients with chronic kidney disease. Cardiovascular risk factors clustering in the metabolic syndrome (MetS) might adversely affect cellular properties. To test the hypothesis that Mets interferes with MSC characteristics, we performed comprehensive comparison of the mRNA, microRNA, and protein content of MSCs isolated from Lean and MetS pigs. Methods: Domestic pigs were fed a 16-week Lean or MetS diet (n = 4 each). Expression profiles of co-existing microRNAs, mRNAs, and proteins were obtained by high-throughput sequencing and liquid chromatography-mass spectrometry. TargetScan and ComiR were used to predict target genes of differentially expressed microRNAs, and DAVID 6.7 for functional annotation analysis to rank primary gene ontology categories for the microRNA target genes, mRNAs, and proteins. Results: Differential expression analysis revealed 12 microRNAs upregulated in MetS-MSCs compared to Lean-MSCs (fold change>1.4, p <.05), which target 7728 genes, whereas 33 mRNAs and 78 proteins were downregulated (fold change<0.7, p <.05). Integrated analysis showed that targets of those microRNAs upregulated in MetS-MSCs overlap with at least half of mRNAs and proteins dysregulated in those cells. Functional analysis of overlapping mRNAs and proteins suggest that they are primarily involved in mitochondria, inflammation and transcription. MetS-MSCs also exhibited increased nuclear translocation of nuclear factor kappa-B, associated with increased SA-β-Galactosidase and decreased cytochrome-c oxidase-IV activity. Conclusion: MetS alters the transcriptome and proteome of swine adipose tissue-derived MSCs particularly genes involved in mitochondria, inflammation and transcription regulation. These alterations might limit the reparative function of endogenous MSC and their use as an exogenous regenerative therapy.",
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AU - Pawar, Aditya S.

AU - Eirin, Alfonso

AU - Krier, James D.

AU - Woollard, John R.

AU - Zhu, Xiang Yang

AU - Lerman, Amir

AU - van Wijnen, Andre J

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AB - Introduction: Mesenchymal stem cells (MSCs) possess endogenous reparative properties and may serve as an exogenous therapeutic intervention in patients with chronic kidney disease. Cardiovascular risk factors clustering in the metabolic syndrome (MetS) might adversely affect cellular properties. To test the hypothesis that Mets interferes with MSC characteristics, we performed comprehensive comparison of the mRNA, microRNA, and protein content of MSCs isolated from Lean and MetS pigs. Methods: Domestic pigs were fed a 16-week Lean or MetS diet (n = 4 each). Expression profiles of co-existing microRNAs, mRNAs, and proteins were obtained by high-throughput sequencing and liquid chromatography-mass spectrometry. TargetScan and ComiR were used to predict target genes of differentially expressed microRNAs, and DAVID 6.7 for functional annotation analysis to rank primary gene ontology categories for the microRNA target genes, mRNAs, and proteins. Results: Differential expression analysis revealed 12 microRNAs upregulated in MetS-MSCs compared to Lean-MSCs (fold change>1.4, p <.05), which target 7728 genes, whereas 33 mRNAs and 78 proteins were downregulated (fold change<0.7, p <.05). Integrated analysis showed that targets of those microRNAs upregulated in MetS-MSCs overlap with at least half of mRNAs and proteins dysregulated in those cells. Functional analysis of overlapping mRNAs and proteins suggest that they are primarily involved in mitochondria, inflammation and transcription. MetS-MSCs also exhibited increased nuclear translocation of nuclear factor kappa-B, associated with increased SA-β-Galactosidase and decreased cytochrome-c oxidase-IV activity. Conclusion: MetS alters the transcriptome and proteome of swine adipose tissue-derived MSCs particularly genes involved in mitochondria, inflammation and transcription regulation. These alterations might limit the reparative function of endogenous MSC and their use as an exogenous regenerative therapy.

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