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MED31 involved in regulating self-renewal and adipogenesis of human mesenchymal stem cells

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Abstract

Regulation of gene expression is critical for the maintenance of cell state and homeostasis. Aberrant regulation of genes can lead to unwanted cell proliferation or misdirected differentiation. Here we investigate the role of MED31, a highly conserved subunit of the Mediator complex, to determine the role this subunit plays in the maintenance of human mesenchymal stem cell (hMSC) state. Using siRNA-mediated knockdown of MED31 we demonstrate a decrease in self-renewal based on cell assays and monitoring of gene expression. In addition, in the absence of MED31, hMSCs also displayed a reduction in adipogenesis as evidenced by diminished lipid vesicle formation and expression of specific adipogenic markers. These data present evidence for a significant role for MED31 in maintaining adult stem cell homeostasis, thereby introducing potential novel targets for future investigation and use in better understanding stem cell behavior and adipogenesis.

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References

  1. Feng J, Mantesso A, De Bari C, Nishiyama A, Sharpe PT (2011) Dual origin of mesenchymal stem cells contributing to organ growth and repair. Proc Natl Acad Sci USA 108:6503–6508

    Article  CAS  Google Scholar 

  2. Le Blanc K, Pittenger MF (2005) Mesenchymal stem cells: progress toward promise. Cytotherapy 7:36–45

    Article  Google Scholar 

  3. Bartholomew A et al (2002) Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 30:42–48

    Article  Google Scholar 

  4. Di Nicola M (2002) Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99:3838–3843

    Article  Google Scholar 

  5. Blazek E, Mittler G, Meisterernst M (2005) The mediator of RNA polymerase II. Chromosoma 113:399–408

    Article  CAS  Google Scholar 

  6. Kagey MH et al (2010) Mediator and cohesin connect gene expression and chromatin architecture. Nature 467:430–435

    Article  CAS  Google Scholar 

  7. Zhao W et al (2013) SIMPL enhancement of tumor necrosis factor-α dependent p65-MED1 complex formation is required for mammalian hematopoietic stem and progenitor cell function. PLoS ONE 8:e61123

    Article  CAS  Google Scholar 

  8. Crawford SE et al (2002) Defects of the heart, eye, and megakaryocytes in peroxisome proliferator activator receptor-binding protein (PBP) null embryos implicate GATA family of transcription factors. J Biol Chem 277:3585–3592

    Article  CAS  Google Scholar 

  9. Wang X, Yang N, Uno E, Roeder RG, Guo S (2006) A subunit of the mediator complex regulates vertebrate neuronal development. Proc Natl Acad Sci USA 103:17284–17289

    Article  CAS  Google Scholar 

  10. Vogl MR et al (2013) Sox10 cooperates with the mediator subunit 12 during terminal differentiation of myelinating glia. J Neurosci 33:6679–6690

    Article  CAS  Google Scholar 

  11. Schwartz CE et al (2007) The original Lujan syndrome family has a novel missense mutation (p.N1007S) in the MED12 gene. J Med Genet 44:472–477

    Article  CAS  Google Scholar 

  12. Risheg H et al (2007) A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome. Nat Genet 39:451–453

    Article  CAS  Google Scholar 

  13. Vulto-van Silfhout AT et al (2013) Mutations in MED12 cause X-linked Ohdo syndrome. Am J Hum Genet 92:401–406

    Article  CAS  Google Scholar 

  14. Zhou H et al (2012) MED12 mutations link intellectual disability syndromes with dysregulated GLI3-dependent Sonic Hedgehog signaling. Proc Natl Acad Sci USA 109:19763–19768

    Article  CAS  Google Scholar 

  15. Ding N et al (2008) Mediator links epigenetic silencing of neuronal gene expression with X-linked mental retardation. Mol Cell 31:347–359

    Article  CAS  Google Scholar 

  16. Schneider M et al (2015) The nuclear pore-associated TREX-2 complex employs mediator to regulate gene expression. Cell 162:1016–1028

    Article  CAS  Google Scholar 

  17. Tsai K-L et al (2014) Subunit architecture and functional modular rearrangements of the transcriptional mediator complex. Cell 157:1430–1444

    Article  CAS  Google Scholar 

  18. Risley MD, Clowes C, Yu M, Mitchell K, Hentges KE (2010) The Mediator complex protein Med31 is required for embryonic growth and cell proliferation during mammalian development. Dev Biol 342:146–156

    Article  CAS  Google Scholar 

  19. Schiano C, Rienzo M, Casamassimi A, Napoli C (2013) Gene expression profile of the whole Mediator complex in human osteosarcoma and normal osteoblasts. Med Oncol 30:739

    Article  Google Scholar 

  20. Jiang C, Chen H, Shao L, Wang Q (2014) MicroRNA-1 functions as a potential tumor suppressor in osteosarcoma by targeting Med1 and Med31. Oncol Rep 32:1249–1256

    Article  CAS  Google Scholar 

  21. Huang DW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank Dr. Bruce Bunnell and his lab for supplying and supporting training in the culturing and characterization of human mesenchymal stem cells. We thank the Research Core Facility Genomics Core at LSU Health Shreveport, which is supported in part by the Center for Cardiovascular Diseases and Sciences, the Center for Molecular and Tumor Virology, and the Feist-Weiller Cancer Center, for their assistance with microarray hybridization, scanning, and initial data analysis. We would like to acknowledge funding support for this project from the Louisiana Biomedical Research Network, an NIH INBRE grant (8P20GM103424), Louisiana Board of Regents Pilot Funding Program, and Louisiana Tech University College of Applied and Natural Sciences and School of Biological Sciences for support of students and purchasing of supplies. Finally, we would like to thank Matthew Busby and Michael Osmun for their help with primer optimization and preliminary data collection.

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Correspondence to Jamie J. Newman.

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The authors do not have any conflict of interest to disclose.

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The GEO accession no is GSE116973 and the link for the GEO dataset to be referenced in the manuscript is as follows: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE116973.

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Beadle, E.P., Straub, J.A., Bunnell, B.A. et al. MED31 involved in regulating self-renewal and adipogenesis of human mesenchymal stem cells. Mol Biol Rep 45, 1545–1550 (2018). https://doi.org/10.1007/s11033-018-4241-5

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  • DOI: https://doi.org/10.1007/s11033-018-4241-5

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