title: Lipopolysaccharide treatment induces genome-wide pre-mRNA splicing pattern changes in mouse bone marrow stromal stem cells.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.|Bioinformatics Program, Indiana University School of Informatics, Indianapolis, IN, 46202, USA.
authors.forename: Ao
authors.initials: A
authors.lastname: Zhou
authors.affiliation: College of Automation, Harbin Engineering University, Harbin, Heilongjiang, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: College of Automation, Harbin Engineering University, Harbin, Heilongjiang, China.
authors.forename: Bo
authors.initials: B
authors.lastname: He
authors.affiliation: College of Automation, Harbin Engineering University, Harbin, Heilongjiang, China.
authors.forename: Weixing
authors.initials: W
authors.lastname: Feng
authors.affiliation: Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Medical and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.|Department of Pharmacology, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
authors.affiliation: Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: A Keith
authors.initials: AK
authors.lastname: Dunker
authors.affiliation: Bioscience Advising, Indianapolis, IN, 46227, USA.
authors.forename: Curt
authors.initials: C
authors.lastname: Balch
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Baiyan
authors.initials: B
authors.lastname: Li
authors.affiliation: Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.|Department of Medical and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medical and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. yuewang@iu.edu.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D005091:Exons / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D020543:Proteome / Q000187:drug effects / Q000235:genetics*; D012326:RNA Splicing / Q000187:drug effects / Q000235:genetics*
chemical_list: D008070:Lipopolysaccharides; D020543:Proteome
keywords: Alternative splicing; Lipopolysaccharide; Mesenchymal stem cells