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Gene and microRNA expression signatures of human mesenchymal stromal cells in comparison to fibroblasts

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Abstract

Human mesenchymal stromal cells (MSCs) offer great hope for the treatment of tissue degenerative and immune diseases, but their phenotypic similarity to dermal fibroblasts may hinder robust cell identification and isolation from diverse tissue harvests. To identify genetic elements that can reliably discriminate MSCs from fibroblasts, we performed comparative gene and microRNA expression profiling analyses with genome-wide oligonucleotide microarrays. When taken globally, both gene and microRNA expression profiles of MSCs were highly similar to those of fibroblasts, accounting well for their extensive phenotypic and functional overlaps. Scattered expression differences were pooled to yield an MSC-specific molecular signature, consisting of 64 genes and 21 microRNAs whose expressions were at least 10-fold and two-fold higher, respectively, in MSCs compared with fibroblasts. Genes either encoding transmembrane proteins or associated with tumors were relatively abundant in this signature. These data should provide the molecular basis not only for the discovery of novel diagnostic markers discriminating MSCs from fibroblasts, but also for further studies on MSC-specific signaling mechanisms.

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References

  • Bao S, Ouyang G, Bai X, Huang Z, Ma C, Liu M, Shao R, Anderson AM, Rich JN, Wang XF (2004) Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt/PKB pathway. Cancer Cell 5:329–339

    Article  PubMed  CAS  Google Scholar 

  • Baskerville S, Barttel DP (2005) Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA 11:241–247

    Article  PubMed  CAS  Google Scholar 

  • Brendel C, Kuklick L, Hartmann O, Kim TD, Boudriot U, Schwell D, Neubauer A (2005) Distinct gene expression profile of human mesenchymal stem cells in comparison to skin fibroblasts employing cDNA microarray analysis of 9600 genes. Gene Expr 12:245–257

    Article  PubMed  CAS  Google Scholar 

  • Bushati N, Cohen SM (2007) MicroRNA functions. Annu Rev Cell Dev Biol 23:175–205

    Article  PubMed  CAS  Google Scholar 

  • Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6:857–866

    Article  PubMed  CAS  Google Scholar 

  • Chang HY, Chi JT, Dudoit S, Bondre C, Rijn M van de, Botstein D, Brown PO (2002) Diversity, topographic differentiation, and positional memory in human fibroblasts. Proc Natl Sci Acad USA 99:12877–12882

    Article  CAS  Google Scholar 

  • Chen CZ, Li L, Lodish HF, Bartel DP (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303:83–86

    Article  PubMed  CAS  Google Scholar 

  • Cheng AM, Byrom MW, Shelton J, Ford LP (2005) Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res 33:1290–1297

    Article  PubMed  CAS  Google Scholar 

  • Darell DK, Kaur S, Stanislaw S, Konieczka JH, Yatskievych TA, Antin PB (2007) MicroRNA expression during chick embryo development. Dev Dyn 235:3156–3165

    Article  CAS  Google Scholar 

  • Dazzi F, Horwood NJ (2007) Potential of mesenchymal stem cell therapy. Curr Opin Oncol 19:650–655

    Article  PubMed  Google Scholar 

  • Dominici M, Le Blanc JK, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop DJ, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317

    Article  PubMed  CAS  Google Scholar 

  • Feldon SE, O’loughlin CW, Ray DM, Landskroner-Eiger S, Seweryniak KE, Phipps RP (2006) Activated human T lymphocytes express cyclooxygenase-2 and produce proadipogenic prostaglandins that drive human orbital fibroblasts differentiation to adipocytes. Am J Pathol 169:1183–1193

    Article  PubMed  CAS  Google Scholar 

  • Fuchs B, Mahlum E, Halder C, Maran A, Yaszemski M, Bode B, Bolander M, Sarkar G (2007) High expression of tumor endothelial marker 7 is associated with metastasis and poor survival of patients with osteogenic sarcoma. Gene 399:137–143

    Article  PubMed  CAS  Google Scholar 

  • Haniffa MA, Wang XN, Holtick U, Rae M, Isaacs JD, Dickinson AM, Hilkens CM, Collin MP (2007) Adult human fibroblasts are potent immunoregulatory cells and functionally equivalent to mesenchymal stem cells. J Immunol 179:1595–1604

    PubMed  CAS  Google Scholar 

  • Hee CK, Jonikas MA, Nicoll SB (2006) Influence of three-dimensional scaffold on the expression of osteogenic differentiation markers by human dermal fibroblasts. Biomaterials 27:875–884

    Article  PubMed  CAS  Google Scholar 

  • Inoue T, Equchi T, Oda Y, Nishiyama K, Fujii K, Izumi H, Kohno K, Yamaquchi K, Tanaka M, Tsuneyoshi M (2007) Expression of GalNAc-T3 and its relationships with clinicopathological factors in 61 extrahepatic bile duct carcinomas analyzed using stepwise sections-special reference to its association with lymph node metastasis. Mod Pathol 20:267–276

    Article  PubMed  CAS  Google Scholar 

  • Ishii M, Koike C, Igarashi A, Yamanaka K, Pan H, Higashi Y, Kawaguchi H, Sugiyama M, Kamata N, Iwata T, Matsubara T, Nakamura K, Kurihara H, Tsuji K, Kato Y (2005) Molecular markers distinguish bone marrow mesenchymal stem cells from fibroblasts. Biochem Biophys Res Comm 332:297–303

    Article  PubMed  CAS  Google Scholar 

  • Javazon EH, Beggs KJ, Flake AW (2004) Mesenchymal stem cells: paradoxes of passaging. Exp Hematol 32:414–425

    Article  PubMed  CAS  Google Scholar 

  • Jelaska A, Strehlow D, Korn JH (1999) Fibroblasts heterogeneity in physiological conditions and fibrotic diseases. Springer Semin Immunopathol 21:385–395

    Article  PubMed  CAS  Google Scholar 

  • Jeong JA, Hong SH, Gang EJ, Ahn C, Hwang SH, Yang IH, Han H, Kim H (2005) Differential gene expression profiling of human umbilical cord blood-derived mesenchymal stem cells by DNA microarray. Stem Cells 23:584–593

    Article  PubMed  CAS  Google Scholar 

  • Jeong JA, Ko KM, Bae S, Jeon CJ, Koh GY, Kim H (2007) Genome-wide differential gene expression profiling of human bone marrow stromal cells. Stem Cells 25:994–1002

    Article  PubMed  CAS  Google Scholar 

  • Johansen JS, Brasso K, Iversen P, Teisner B, Garnero P, Price PA, Christensen IJ (2007) Changes of biochemical markers of bone turnover and YKL-40 following hormonal treatment for metastatic prostate cancer are related to survival. Clin Cancer Res 13:3244–3249

    Article  PubMed  CAS  Google Scholar 

  • Keating A (2006) Mesenchymal stromal cells. Curr Opin Hematol 13:419–425

    Article  PubMed  Google Scholar 

  • Kim VN, Nam JW (2006) Genomics of microRNA. Trend Genet 22:165–173

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Liang Y, Ridzon D, Wong L, Chen C (2007) Characterization of microRNA expression profiles in normal human tissues. BMC Genomics 8:166

    Article  PubMed  CAS  Google Scholar 

  • Lysy PA, Smets F, Sibille C, Najimi M, Sokal EM (2007) Human skin fibroblasts: from mesodermal to heptatocyte-like differentiation. Hepatol 46:1574–1585

    Article  CAS  Google Scholar 

  • Phillips JE, Hutmacher DW, Guldgerg RE, Garcia AJ (2006) Mineralization capacity of Runx2/Cbfa1-genetically engineered fibroblasts is scaffold dependent. Biomaterials 27:5535–5545

    Article  PubMed  CAS  Google Scholar 

  • Rinn JL, Bondre C, Gladstone HB, Brown PO, Chang HY (2006) Anatomic demarcation by positional variation in fibroblast gene expression programs. PloS Genet 2:1084–1096

    Article  CAS  Google Scholar 

  • Rutherford RB, Gu K, Racenis P, Krebsbach PH (2003) Early events: the in vitro conversion of BMP transduced fibroblasts to chondroblasts. Connect Tissue Res 44:117–123

    Article  PubMed  CAS  Google Scholar 

  • Sabatini F, Petecchia L, Tavian M, de Villeroche VJ, Rossi GA, Brouty-Boye D (2005) Human bronchial fibroblasts exhibit a mesenchymal stem cell phenotype and multilineage differentiating potentialities. Lab Invest 85:962–971

    Article  PubMed  CAS  Google Scholar 

  • Silva Meirelles L da, Chagastelles PC, Nardi NB (2006) Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci 119:2204–2213

    Article  PubMed  CAS  Google Scholar 

  • Sullivan CS, Ganem D (2005) MicroRNAs and viral infection. Mol Cell 20:3–7

    Article  PubMed  CAS  Google Scholar 

  • Tavazoie SF, Alarcon C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL, Massague J (2008) Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451:147–152

    Article  PubMed  CAS  Google Scholar 

  • Tocci A, Forte L (2003) Mesenchymal stem cell: use and perspectives. Hematol J 4:92–96

    Article  PubMed  Google Scholar 

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Correspondence to Hoeon Kim.

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Sohyun Bae and Jung Hoon Ahn contributed equally to this work.

This research was supported in part by a grant (SC-2140) from Stem Cell Research Center of the 21st Century Frontier Research Program, and in part by Korea Science and Engineering Foundation grant (M10641000037) funded by the Ministry of Education, Science and Technology, Republic of Korea.

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Supplementary Table 1

Gene expression signature of MSCs in comparison with fibroblasts (DOC 111 KB)

Supplementary Table 2

Hybridization intensity ratio of microRNAs (XLS 64 KB)

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Bae, S., Ahn, J.H., Park, C.W. et al. Gene and microRNA expression signatures of human mesenchymal stromal cells in comparison to fibroblasts. Cell Tissue Res 335, 565–573 (2009). https://doi.org/10.1007/s00441-008-0729-y

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