Lipopolysaccharide treatment induces genome-wide pre-mRNA splicing pattern changes in mouse bone marrow stromal stem cells

Ao Zhou, Meng Li, Bo He, Weixing Feng, Fei Huang, Bing Xu, A. Dunker, Curt Balch, Baiyan Li, Yunlong Liu, Yue Wang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Lipopolysaccharide (LPS) is a gram-negative bacterial antigen that triggers a series of cellular responses. LPS pre-conditioning was previously shown to improve the therapeutic efficacy of bone marrow stromal cells/bone-marrow derived mesenchymal stem cells (BMSCs) for repairing ischemic, injured tissue. Results: In this study, we systematically evaluated the effects of LPS treatment on genome-wide splicing pattern changes in mouse BMSCs by comparing transcriptome sequencing data from control vs. LPS-treated samples, revealing 197 exons whose BMSC splicing patterns were altered by LPS. Functional analysis of these alternatively spliced genes demonstrated significant enrichment of phosphoproteins, zinc finger proteins, and proteins undergoing acetylation. Additional bioinformatics analysis strongly suggest that LPS-induced alternatively spliced exons could have major effects on protein functions by disrupting key protein functional domains, protein-protein interactions, and post-translational modifications. Conclusion: Although it is still to be determined whether such proteome modifications improve BMSC therapeutic efficacy, our comprehensive splicing characterizations provide greater understanding of the intracellular mechanisms that underlie the therapeutic potential of BMSCs.

Original languageEnglish (US)
Article number509
JournalBMC Genomics
Volume17
DOIs
StatePublished - Aug 22 2016

Fingerprint

RNA Precursors
Mesenchymal Stromal Cells
Lipopolysaccharides
Stem Cells
Genome
Bone Marrow
Exons
Proteins
Bacterial Antigens
Recombinant DNA
Phosphoproteins
Zinc Fingers
Proteome
Post Translational Protein Processing
Acetylation
Computational Biology
Transcriptome
Therapeutics

Keywords

  • Alternative splicing
  • Lipopolysaccharide
  • Mesenchymal stem cells

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Lipopolysaccharide treatment induces genome-wide pre-mRNA splicing pattern changes in mouse bone marrow stromal stem cells. / Zhou, Ao; Li, Meng; He, Bo; Feng, Weixing; Huang, Fei; Xu, Bing; Dunker, A.; Balch, Curt; Li, Baiyan; Liu, Yunlong; Wang, Yue.

In: BMC Genomics, Vol. 17, 509, 22.08.2016.

Research output: Contribution to journalArticle

Zhou, Ao ; Li, Meng ; He, Bo ; Feng, Weixing ; Huang, Fei ; Xu, Bing ; Dunker, A. ; Balch, Curt ; Li, Baiyan ; Liu, Yunlong ; Wang, Yue. / Lipopolysaccharide treatment induces genome-wide pre-mRNA splicing pattern changes in mouse bone marrow stromal stem cells. In: BMC Genomics. 2016 ; Vol. 17.
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AU - Xu, Bing

AU - Dunker, A.

AU - Balch, Curt

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AB - Background: Lipopolysaccharide (LPS) is a gram-negative bacterial antigen that triggers a series of cellular responses. LPS pre-conditioning was previously shown to improve the therapeutic efficacy of bone marrow stromal cells/bone-marrow derived mesenchymal stem cells (BMSCs) for repairing ischemic, injured tissue. Results: In this study, we systematically evaluated the effects of LPS treatment on genome-wide splicing pattern changes in mouse BMSCs by comparing transcriptome sequencing data from control vs. LPS-treated samples, revealing 197 exons whose BMSC splicing patterns were altered by LPS. Functional analysis of these alternatively spliced genes demonstrated significant enrichment of phosphoproteins, zinc finger proteins, and proteins undergoing acetylation. Additional bioinformatics analysis strongly suggest that LPS-induced alternatively spliced exons could have major effects on protein functions by disrupting key protein functional domains, protein-protein interactions, and post-translational modifications. Conclusion: Although it is still to be determined whether such proteome modifications improve BMSC therapeutic efficacy, our comprehensive splicing characterizations provide greater understanding of the intracellular mechanisms that underlie the therapeutic potential of BMSCs.

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