Skip to main content
SpringerLink
Log in

Differentiation of single cell derived human mesenchymal stem cells into cells with a neuronal phenotype: RNA and microRNA expression profile

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

The adult bone marrow contains a subset of non-haematopoietic cells referred to as bone marrow mesenchymal stem cells (BMSCs). Mesenchymal stem cells (MSCs) have attracted immense research interest in the field of regenerative medicine due to their ability to be cultured for successive passages and multi-lineage differentiation. The molecular mechanisms governing the self-renewal and differentiation of MSCs remain largely unknown. In a previous paper we demonstrated the ability to induce human clonal MSCs to differentiate into cells with a neuronal phenotype (DMSCs). In the present study we evaluated gene expression profiles by Sequential Analysis of Gene Expression (SAGE) and microRNA expression profiles before and after the neuronal differentiation process. Various tissue-specific genes were weakly expressed in MSCs, including those of non-mesodermal origin, suggesting multiple potential tissue-specific differentiation, as well as stemness markers. Expression of OCT4, KLF4 and c-Myc cell reprogramming factors, which are modulated during the differentiation process, was also observed. Many peculiar nervous tissue genes were expressed at a high level in DMSCs, along with genes related to apoptosis. MicroRNA profiling and correlation with mRNA expression profiles allowed us to identify putative important genes and microRNAs involved in the differentiation of MSCs into neuronal-like cells. The profound difference in gene and microRNA expression patterns between MSCs and DMSCs indicates a real functional change during differentiation from MSCs to DMSCs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mezey E, Chandross KJ, Harta G, Maki RA, McKercher SR (2000) Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 290(5497):1779–1782

    Article  PubMed  CAS  Google Scholar 

  2. Brazelton TR, Rossi FM, Keshet GI, Blau HM (2000) From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290(5497):1775–1779

    Article  PubMed  CAS  Google Scholar 

  3. Prockop DJ (2009) Repair of tissues by adult stem/progenitor cells (MSCs): controversies, myths, and changing paradigms. Mol Ther 17(6):939–946

    Article  PubMed  CAS  Google Scholar 

  4. Liechty KW, MacKenzie TC, Shaaban AF, Radu A, Moseley AM, Deans R, Marshak DR, Flake AW (2000) Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 2000(6):1282–1286

    Google Scholar 

  5. Kumar S, Chanda D, Ponnazhagan S (2008) Therapeutic potential of genetically modified mesenchymal stem cells. Gene Ther 15:711–715

    Article  PubMed  CAS  Google Scholar 

  6. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418(6893):41–49

    Article  PubMed  CAS  Google Scholar 

  7. Mazzini L, Ferrero I, Luparello V, Rustichelli D, Gunetti M, Mareschi K, Testa L, Stecco A, Tarletti R, Miglioretti M, Fava E, Nasuelli N, Cisari C, Massara M, Vercelli R, Oggioni GD, Carriero A, Cantello R, Monaco F, Fagioli F (2010) Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: a phase I clinical trial. Exp Neurol 223(1):229–237

    Article  PubMed  CAS  Google Scholar 

  8. Sugaya K, Merchant S (2008) How to approach Alzheimer’s disease therapy using stem cell technologies. J Alzheimers Dis 15(2):241–254

    PubMed  CAS  Google Scholar 

  9. Sadan O, Shemesh N, Cohen Y, Melamed E, Offen D (2009) Adult neurotrophic factor-secreting stem cells: a potential novel therapy for neurodegenerative diseases. Isr Med Assoc J 11:201–204

    PubMed  Google Scholar 

  10. Strauer BE, Schannwell CM, Brehm M (2009) Therapeutic potentials of stem cells in cardiac diseases. Minerva Cardioangiol 57(2):249–267

    PubMed  CAS  Google Scholar 

  11. Xu W, Zhang X, Qian H, Zhu W, Sun X, Hu J, Zhou H, Chen Y (2004) Mesenchymal stem cells from adult human bone marrow differentiate into a cardiomyocyte phenotype in vitro. Exp Biol Med 229:623–631

    CAS  Google Scholar 

  12. Pedemonte E, Benvenuto F, Casazza S, Mancardi G, Oksenberg JR, Uccelli A, Baranzini S (2007) The molecular signature of therapeutic mesenchymal stem cells exposes the architecture of the hematopoietic stem cell niche synapse. BMC Genomics 8:65

    Article  PubMed  Google Scholar 

  13. Uccelli A, Moretta L, Pistoia V (2008) Mesenchymal stem cells in health and disease. Nat Rev Immunol 8:726–736

    Article  PubMed  CAS  Google Scholar 

  14. Uccelli A, Prockop DJ (2010) Why should mesenchymal stem cells (MSCs) cure autoimmune diseases? Curr Opin Immunol 22:768–774

    Article  PubMed  CAS  Google Scholar 

  15. Uccelli A, Morando S, Bonanno S, Bonanni I, Leonardi A, Mancardi G (2011) Mesenchymal stem cells for multiple sclerosis: does neural differentiation really matter? Curr Stem Cell Res Ther 6:69–72

    Article  PubMed  CAS  Google Scholar 

  16. Scintu F, Reali C, Pillai R, Badiali M, Sanna MA, Argiolu F, Ristaldi MS, Sogos V (2006) Differentiation of human bone marrow stem cells into cells with a neural phenotype: diverse effects of two specific treatments. BMC Neurosci 16:7–14

    Google Scholar 

  17. Velculescu VE, Zhang L, Vogelstein B, Kinzler KW (1995) Serial analysis of gene expression. Science 270(5235):484–487

    Article  PubMed  CAS  Google Scholar 

  18. Christensen M, Schratt GM (2009) microRNA involvement in developmental and functional aspects of the nervous system and in neurological diseases. Neurosci Lett 466(2):55–62

    Article  PubMed  CAS  Google Scholar 

  19. Siegel G, Obernosterer G, Fiore R, Oehmen M, Bicker S, Christensen M, Khudayberdiev S, Leuschner PF, Busch CJ, Kane C, Hübel K, Dekker F, Hedberg C, Rengarajan B, Drepper C, Waldmann H, Kauppinen S, Greenberg ME, Draguhn A, Rehmsmeier M, Martinez J, Schratt GM (2009) A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis. Nat Cell Biol 11:705–716

    Article  PubMed  CAS  Google Scholar 

  20. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    Article  PubMed  CAS  Google Scholar 

  21. Bruneel A, Labas V, Mailloux A, Sharma S, Royer N, Vinh J, Pernet P, Vaubourdolle M, Baudin B (2005) Proteomics of human umbilical vein endothelial cells applied to etoposide-induced apoptosis. Proteomics 5:3876–3884

    Article  PubMed  CAS  Google Scholar 

  22. Toyama S, Toyama S (1984) A variant form of beta-actin in a mutant of KB cells resistant to cytochalasin B. Cell 37:609–614

    Article  PubMed  CAS  Google Scholar 

  23. He YY, Council SE, Feng L, Chignell CF (2008) UVA-induced cell cycle progression is mediated by a disintegrin and metalloprotease/epidermal growth factor receptor/AKT/Cyclin D1 pathways in keratinocytes. Cancer Res 15:3752–3758

    Article  Google Scholar 

  24. Scalia P, Heart E, Comai L, Vigneri R, Sung CK (2001) Regulation of the Akt/Glycogen synthase kinase-3 axis by insulin-like growth factor-II via activation of the human insulin receptor isoform-A. J Cell Biochem 82:610–618

    Article  PubMed  CAS  Google Scholar 

  25. De Chiara TM, Robertson EJ, Efstratiadis A (1991) Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64:849–859

    Article  Google Scholar 

  26. Santamaría A, Castellanos E, Gómez V, Benedit P, Renau-Piqueras J, Morote J, Reventós J, Thomson TM, Paciucci R (2005) PTOV1 enables the nuclear translocation and mitogenic activity of flotillin-1, a major protein of lipid rafts. Mol Cell Biol 25:1900–1911

    Article  PubMed  Google Scholar 

  27. Cicha I, Goppelt-Struebe M (2009) Connective tissue growth factor: context-dependent functions and mechanisms of regulation. Biofactors 35:200–208

    Article  PubMed  CAS  Google Scholar 

  28. Muragaki Y, Mattei MG, Yamaguchi N, Olsen BR, Ninomiya Y (1991) The complete primary structure of the human alpha 1 (VIII) chain and assignment of its gene (COL8A1) to chromosome 3. Eur J Biochem 197:615–622

    Article  PubMed  CAS  Google Scholar 

  29. Kim YM, Kim EC, Kim Y (2011) The human lysyl oxidase-like 2 protein functions as an amine oxidase toward collagen and elastin. Mol Biol Rep 38(1):145–149

    Article  PubMed  CAS  Google Scholar 

  30. Rupp H, Maisch B (2007) Separation of large mammalian ventricular myosin differing in ATPase activity. Can J Physiol Pharmacol 85:326–331

    Article  PubMed  CAS  Google Scholar 

  31. Takahashi S, Reddy SV, Chirgwin JM, Devlin R, Haipek C, Anderson J, Roodman GD (1994) Cloning and identification of annexin II as an autocrine/paracrine factor that increases osteoclast formation and bone resorption. J Biol Chem 269:28696–28701

    PubMed  CAS  Google Scholar 

  32. Mizukami Y, Ono K, Du CK, Aki T, Hatano N, Okamoto Y, Ikeda Y, Ito H, Hamano K, Morimoto S (2008) Identification and physiological activity of survival factor released from cardiomyocytes during ischaemia and reperfusion. Cardiovasc Res 79:589–599

    Article  PubMed  CAS  Google Scholar 

  33. Tiso N, Rampoldi L, Pallavicini A, Zimbello R, Pandolfo D, Valle G, Lanfranchi G, Danieli GA (1997) Fine mapping of five human skeletal muscle genes: alpha-tropomyosin, beta-tropomyosin, troponin-I slow-twitch, troponin-I fast-twitch, and troponin-C fast. Biochem Biophys Res Commun 230:347–350

    Article  PubMed  CAS  Google Scholar 

  34. Hirata H, Tatsumi H, Sokabe M (2008) Mechanical forces facilitate actin polymerization at focal adhesions in a zyxin-dependent manner. J Cell Sci 121:2795–2804

    Article  PubMed  CAS  Google Scholar 

  35. Mohan RR, Mohan RR, Wilson SE (2001) Discoidin domain receptor (DDR) 1 and 2: collagen-activated tyrosine kinase receptors in the cornea. Exp Eye Res 72:87–92

    Article  PubMed  CAS  Google Scholar 

  36. Liu Y, Monticone M, Tonachini L, Mastrogiacomo M, Marigo V, Cancedda R, Castagnola P (2004) URB expression in human bone marrow stromal cells and during mouse development. Biochem Biophys Res Commun 322:497–507

    Article  PubMed  CAS  Google Scholar 

  37. Furusawa T, Lim JH, Catez F, Birger Y, Mackem S, Bustin M (2006) Down-regulation of nucleosomal binding protein HMGN1 expression during embryogenesis modulates Sox9 expression in chondrocytes. Mol Cell Biol 26:592–604

    Article  PubMed  CAS  Google Scholar 

  38. Bot PT, Hoefer IE, Sluijter JP, van Vliet P, Smits AM, Lebrin F, Moll F, de Vries JP, Doevendans P, Piek JJ, Pasterkamp G, Goumans MJ (2009) Increased expression of the transforming growth factor-beta signaling pathway, endoglin, and early growth response-1 in stable plaques. Stroke 40:439–447

    Article  PubMed  CAS  Google Scholar 

  39. Tanaka SM, Sun HB, Roeder RK, Burr DB, Turner CH, Yokota H (2005) Osteoblast responses one hour after load-induced fluid flow in a three-dimensional porous matrix. Calcif Tissue Int 76:261–271

    Article  PubMed  CAS  Google Scholar 

  40. Hamamura K, Weng Y, Zhao J, Yokota H, Xie D (2008) PEG attachment to osteoblasts enhances mechanosensitivity. Biomed Mater 3:25017

    Article  Google Scholar 

  41. Pena AN, Pereira-Smith OM (2007) The role of the MORF/MRG family of genes in cell growth, differentiation, DNA repair, and thereby aging. Ann N Y Acad Sci 1100:299–305

    Article  PubMed  CAS  Google Scholar 

  42. Bortoluzzi S, d’Alessi F, Romualdi C, Danieli GA (2001) Differential expression of genes coding for ribosomal proteins in different human tissues. Bioinformatics 17:1152–1157

    Article  PubMed  CAS  Google Scholar 

  43. Hendershot LM, Valentine VA, Lee AS, Morris SW, Shapiro DN (1994) Localization of the gene encoding human BiP/GRP78, the endoplasmic reticulum cognate of the HSP70 family, to chromosome 9q34. Genomics 20:281–284

    Article  PubMed  CAS  Google Scholar 

  44. Thomas TZ, Wang H, Niclasen P, O’Bryan MK, Evans LW, Groome NP, Pedersen J, Risbridger GP (1997) Expression and localization of activin subunits and follistatins in tissues from men with high grade prostate cancer. J Clin Endocrinol Metab 82:3851–3858

    Article  PubMed  CAS  Google Scholar 

  45. Kleeff J, Ishiwata T, Friess H, Büchlor MW, Koro M (1998) Concomitant over-expression of activin/inhibin beta subunits and their receptors in human pancreatic cancer. Int J Cancer 77:860–868

    Article  PubMed  CAS  Google Scholar 

  46. Zheng W, Luo MP, Welt C, Lambert-Messerlian G, Sung CJ, Zhang Z, Ying SY, Schneyer AL, Lauchlan SC, Felix JC (1998) Imbalanced expression of inhibin and activin subunits in primary epithelial ovarian cancer. Gynecol Oncol 69:23–31

    Article  PubMed  CAS  Google Scholar 

  47. Wildi S, Kleeff J, Maruyama H, Maurer CA, Buchler MW, Korc M (2001) Overexpression of activin A in stage IV colorectal cancer. Gut 49:409–417

    Article  PubMed  CAS  Google Scholar 

  48. D’Amour KA, Agulnick AD, Eliazer S, Kelly OG, Kroon E, Baetge EE (2005) Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat Biotechnol 23:1534–1541

    Article  PubMed  Google Scholar 

  49. Zhou Y, Zhong Y, Wang Y, Zhang X, Batista DL, Gejman R, Ansell PJ, Zhao J, Weng C, Klibanski A (2007) Activation of p53 by MEG3 non-coding RNA. J Biol Chem 282:24731–24742

    Article  PubMed  CAS  Google Scholar 

  50. Sierko E, Wojtukiewicz MZ, Kisiel W (2007) The role of tissue factor pathway inhibitor-2 in cancer biology. Semin Thromb Hemost 33:653–659

    Article  PubMed  CAS  Google Scholar 

  51. Nishimura K, Yoshihara F, Tojima T, Ooashi N, Yoon W, Mikoshiba K, Bennett V, Kamiguchi H (2003) L1-dependent neuritogenesis involves ankyrinB that mediates L1-CAM coupling with retrograde actin flow. J Cell Biol 163:1077–1088

    Article  PubMed  CAS  Google Scholar 

  52. Kunimoto M, Otto E, Bennett V (1991) A new 440-kD isoform is the major ankyrin in neonatal rat brain. J Cell Biol 115:1319–1331

    Article  PubMed  CAS  Google Scholar 

  53. Chan W, Kordeli E, Bennett V (1993) 440-kD ankyrin-B: structure of the major developmentally regulated domain and selective localization in unmyelinated axons. J Cell Biol 123:1463–1473

    Article  PubMed  CAS  Google Scholar 

  54. Mosevitsky MI (2005) Nerve ending “signal” proteins GAP-43, MARCKS, and BASP1. Int Rev Cytol 245:245–325

    Article  PubMed  CAS  Google Scholar 

  55. Aberg K, Saetre P, Jareborg N, Jazin E (2006) Human QKI, a potential regulator of mRNA expression of human oligodendrocyte-related genes involved in schizophrenia. Proc Natl Acad Sci USA 103:7482–7487

    Article  PubMed  Google Scholar 

  56. Utreras E, Jiménez-Mateos EM, Contreras-Vallejos E, Tortosa E, Pérez M, Rojas S, Saragoni L, Maccioni RB, Avila J, González-Billault C (2008) Microtubule-associated protein 1B interaction with tubulin tyrosine ligase contributes to the control of microtubule tyrosination. Dev Neurosci 30:200–210

    Article  PubMed  CAS  Google Scholar 

  57. Dompierre JP, Godin JD, Charrin BC, Cordelières FP, King SJ, Humbert S, Saudou F (2007) Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington’s disease by increasing tubulin acetylation. J Neurosci 27:3571–3583

    Article  PubMed  CAS  Google Scholar 

  58. Praticò D, Zhukareva V, Yao Y, Uryu K, Funk CD, Lawson JA, Trojanowski JQ, Lee VM (2004) 12/15-lipoxygenase is increased in Alzheimer’s disease: possible involvement in brain oxidative stress. Am J Pathol 164:1655–1662

    Article  PubMed  Google Scholar 

  59. Potluri P, Davila A, Ruiz-Pesini E, Mishmar D, O’Hearn S, Hancock S, Simon M, Scheffler IE, Wallace DC, Procaccio V (2009) A novel NDUFA1 mutation leads to a progressive mitochondrial complex I-specific neurodegenerative disease. Mol Genet Metab 96:189–195

    Article  PubMed  CAS  Google Scholar 

  60. Tretter L, Sipos I, Adam-Vizi V (2004) Initiation of neuronal damage by complex I deficiency and oxidative stress in Parkinson’s disease. Neurochem Res 29:569–577

    Article  PubMed  CAS  Google Scholar 

  61. Huang J, Xu LG, Liu T, Zhai Z, Shu HB (2006) The p53-inducible E3 ubiquitin ligase p53RFP induces p53-dependent apoptosis. FEBS Lett 580:940–947

    Article  PubMed  CAS  Google Scholar 

  62. Kao YR, Shih JY, Wen WC, Ko YP, Chen BM, Chan YL, Chu YW, Yang PC, Wu CW, Roffler SR (2003) Tumor-associated antigen L6 and the invasion of human lung cancer cells. Clin Cancer Res 9:2807–2816

    PubMed  CAS  Google Scholar 

  63. Andree H, Thiele H, Fähling M, Schmidt I, Thiele BJ (2006) Expression of the human TPT1 gene coding for translationally controlled tumor protein (TCTP) is regulated by CREB transcription factors. Gene 380:95–103

    Article  PubMed  CAS  Google Scholar 

  64. Tuynder M, Fiucci G, Prieur S, Lespagnol A, Géant A, Beaucourt S, Duflaut D, Besse S, Susini L, Cavarelli J, Moras D, Amson R, Telerman A (2004) Translationally controlled tumor protein is a target of tumor reversion. Proc Natl Acad Sci USA 101:15364–15369

    Article  PubMed  CAS  Google Scholar 

  65. Zhang W, Hawse J, Huang Q, Sheets N, Miller KM, Horwitz J, Kantorow M (2002) Decreased expression of ribosomal proteins in human age-related cataract. Invest Ophthalmol Vis Sci 43:198–204

    PubMed  Google Scholar 

  66. Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY (2007) miR-21-mediated tumor growth. Oncogene 26:2799–2803

    Article  PubMed  CAS  Google Scholar 

  67. Karanu FN, Murdoch B, Gallacher L, Wu DM, Koremoto M, Sakano S, Bhatia M (2000) The notch ligand jagged-1 represents a novel growth factor of human hematopoietic stem cells. J Exp Med 192:1365–1372

    Article  PubMed  CAS  Google Scholar 

  68. Lindsell CE, Shawber CJ, Boulter J, Weinmaster G (1995) Jagged: a mammalian ligand that activates Notch1. Cell 80:909–917

    Article  PubMed  CAS  Google Scholar 

  69. Hashimi ST, Fulcher JA, Chang MH, Gov L, Wang S, Lee B (2009) MicroRNA profiling identifies miR-34a and miR-21 and their target genes JAG1 and WNT1 in the coordinate regulation of dendritic cell differentiation. Blood 114:404–414

    Article  PubMed  CAS  Google Scholar 

  70. Perry SV (2001) Vertebrate tropomyosin: distribution, properties and function. J Muscle Res Cell Motil 22:5–49

    Article  PubMed  CAS  Google Scholar 

  71. Lütolf S, Radtke F, Aguet M, Suter U, Taylor V (2002) Notch1 is required for neuronal and glial differentiation in the cerebellum. Development 129:373–385

    PubMed  Google Scholar 

  72. Woo SM, Kim J, Han HW, Chae JI, Son MY, Cho S, Chung HM, Han YM, Kang YK (2009) Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells. BMC Neurosci 10:97

    Article  PubMed  Google Scholar 

  73. Akao Y, Nakagawa Y, Hirata I, Iio A, Itoh T, Kojima K, Nakashima R, Kitade Y, Naoe T (2010) Role of anti-oncomirs miR-143 and -145 in human colorectal tumors. Cancer Gene Ther 17(6):398–408

    Article  PubMed  CAS  Google Scholar 

  74. Tremain N, Korkko J, Ibberson D, Kopen GC, DiGirolamo C, Phinney DG (2001) MicroSAGE analysis of 2,353 expressed genes in a single cell-derived colony of undifferentiated human mesenchymal stem cells reveals mRNAs of multiple cell lineages. Stem Cells 19:408–418

    Article  PubMed  CAS  Google Scholar 

  75. Dagai L, Peri-Naor R, Birk RZ (2009) Docosahexaenoic acid significantly stimulates immediate early response genes and neurite outgrowth. Neurochem Res 34:867–875

    Article  PubMed  CAS  Google Scholar 

  76. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705

    Article  PubMed  CAS  Google Scholar 

  77. Parr AM, Tator CH, Keating A (2007) Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury. Bone Marrow Transplant 40:609–619

    Article  PubMed  CAS  Google Scholar 

  78. Djouad F et al (2003) Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood 102:3837–3844

    Article  PubMed  CAS  Google Scholar 

  79. Karnoub AE et al (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449:557–563

    Article  PubMed  CAS  Google Scholar 

  80. Rubio D et al (2005) Spontaneous human adult stem cell transformation. Cancer Res 65:3035–3039

    PubMed  CAS  Google Scholar 

  81. Tolar J et al (2006) Sarcoma derived from cultured mesenchymal stem cells. Stem Cells 25:371–379

    Article  PubMed  Google Scholar 

  82. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  PubMed  CAS  Google Scholar 

  83. Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, Pfeffer S, Rice A, Kamphorst AO, Landthaler M, Lin C, Socci ND, Hermida L, Fulci V, Chiaretti S, Foà R, Schliwka J, Fuchs U, Novosel A, Müller RU, Schermer B, Bissels U, Inman J, Phan Q, Chien M, Weir DB, Choksi R, De Vita G, Frezzetti D, Trompeter HI, Hornung V, Teng G, Hartmann G, Palkovits M, Di Lauro R, Wernet P, Macino G, Rogler CE, Nagle JW, Ju J, Papavasiliou FN, Benzing T, Lichter P, Tam W, Brownstein MJ, Bosio A, Borkhardt A, Russo JJ, Sander C, Zavolan M, Tuschl T (2007) A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129:1401–1414

    Article  PubMed  CAS  Google Scholar 

  84. Jiang J, Chan YS, Loh YH, Cai J, Tong GQ, Lim CA, Robson P, Zhong S, Ng HH (2008) A core Klf circuitry regulates self-renewal of embryonic stem cells. Nat Cell Biol 10:353–360

    Article  PubMed  Google Scholar 

  85. George AJ, Gordon L, Beissbarth T, Koukoulas I, Holsinger RM, Perreau V, Cappai R, Tan SS, Masters CL, Scott HS, Li QX (2009) A serial analysis of gene expression profile of the Alzheimer’s disease Tg2576 mouse model. Neurotox Res 17:360–379

    Article  PubMed  Google Scholar 

  86. Mendiburu CF, Silva WA Jr, Ricci O Jr, Bonini-Domingos CR, Fett-Conte AC (2008) Global gene expression profile in myelodysplastic syndromes using SAGE. Genet Mol Res 7:1245–1250

    Article  PubMed  CAS  Google Scholar 

  87. Mareschi K, Novara M, Rustichelli D, Ferrero I, Guido D, Carbone M, Medico E, Madon E, Vercelli A, Fagioli F (2006) Neural differentiation of human mesenchymal stem cells: evidence for expression of neural markers and eag K+ cannel types. Exp Hematol 34:1563–1572

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Istituto di Ricerca Genetica e Biomedica (IRGB), del Consiglio Nazionale delle Ricerche (CNR), Cittadella Universitaria di Cagliari, S.S. 554 bivio per Sestu, 09042, Monserrato, CA, Italy

    Francesca Crobu, Veronica Latini, Maria Franca Marongiu, Susanna Porcu, Carla Casu, Maria Francesca Manchinu & Maria Serafina Ristaldi

  2. Dipartimento di Citomorfologia, Facoltà di Medicina, Università di Cagliari, Monserrato, CA, Italy

    Valeria Sogos & Franca Scintu

  3. Ospedale Regionale per le Microcitemie, Cagliari, Italy

    Manuela Badiali & Adele Sanna

Authors
  1. Francesca Crobu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Veronica Latini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Franca Marongiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Valeria Sogos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Franca Scintu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Susanna Porcu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Carla Casu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Manuela Badiali
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Adele Sanna
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Maria Francesca Manchinu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Maria Serafina Ristaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria Serafina Ristaldi.

Additional information

This paper is dedicated to the memory of Dr. Adele Sanna.

Francesca Crobu, Veronica Latini, Maria Franca Marongiu contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 4299 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Crobu, F., Latini, V., Marongiu, M.F. et al. Differentiation of single cell derived human mesenchymal stem cells into cells with a neuronal phenotype: RNA and microRNA expression profile. Mol Biol Rep 39, 3995–4007 (2012). https://doi.org/10.1007/s11033-011-1180-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-011-1180-9

Keywords

Search

Navigation