Cell and Tissue Research

, Volume 331, Issue 1, pp 57–66

microRNA and stem cell function

Review

Abstract

The identification and characterization of stem cells for various tissues has led to a greater understanding of development, tissue maintenance, and cancer pathology. Stem cells possess the ability to divide throughout their life and to produce differentiated daughter cells while maintaining a population of undifferentiated cells that remain in the stem cell niche and that retain stem cell identity. Many cancers also have small populations of cells with stem cell characteristics. These cells have been called cancer stem cells and are a likely cause of relapse in cancer patients. Understanding the biology of stem cells and cancer stem cells offers great promise in the fields of regenerative medicine and cancer treatment. microRNAs (miRNAs) are emerging as important regulators of post-transcriptional gene expression and are considered crucial for proper stem cell maintenance and function. miRNAs have also been strongly implicated in the development and pathology of cancer. In this review, we discuss the characteristics of various stem cell types, including cancer stem cells, and the importance of miRNAs therein.

Keywords

Stem cells microRNA Cancer Regulators Self-renewal Division Maintenance 

References

  1. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–3988PubMedGoogle Scholar
  2. Aravin A, Gaidatzis D, Pfeffer S, Lagos-Quintana M, Landgraf P, Iovino N, Morris P, Brownstein MJ, Kuramochi-Miyagawa S, Nakano T, Chien M, Russo JJ, Ju J, Sheridan R, Sander C, Zavolan M, Tuschl T (2006) A novel class of small RNAs bind to MILI protein in mouse testes. Nature 442:203–207PubMedGoogle Scholar
  3. Aravin AA, Sachidanandam R, Girard A, Fejes-Toth K, Hannon GJ (2007) Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 316:744–747PubMedGoogle Scholar
  4. Babaie Y, Herwig R, Greber B, Brink TC, Wruck W, Groth D, Lehrach H, Burdon T, Adjaye J (2007) Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells. Stem Cells 25:500–510PubMedGoogle Scholar
  5. Bar EE, Chaudhry A, Lin A, Fan X, Schreck K, Matsui W, Vescovi AL, Piccirillo S, Dimeco F, Olivi A, Eberhart CG (2007) Cyclopamine-mediated Hedgehog pathway inhibition depletes stem-like cancer cells in gioblastoma. Stem Cells 25:2524–2533PubMedGoogle Scholar
  6. Behm-Ansmant I, Rehwinkel J, Doerks T, Stark A, Bork P, Izaurralde E (2006) mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes. Genes Dev 20:1885–1898PubMedGoogle Scholar
  7. Bendall SC, Stewart MH, Menendez P, George D, Vijayaragavan K, Werbowetski-Ogilvie T, Ramos-Mejia V, Rouleau A, Yang J, Bosse M, Lajoie G, Bhatia M (2007) IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro. Nature 448:1015–1021PubMedGoogle Scholar
  8. Bernstein E, Caudy AA, Hammond SM, Hannon GJ (2001) Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409:363–366PubMedGoogle Scholar
  9. Bernstein E, Kim SY, Carmell MA, Murchison EP, Alcorn H, Li MZ, Mills AA, Elledge SJ, Anderson KV, Hannon GJ (2003) Dicer is essential for mouse development. Nat Genet 35:215–217PubMedGoogle Scholar
  10. Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber SL, Lander ES (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125:315–326PubMedGoogle Scholar
  11. Boiani M, Scholer HR (2005) Regulatory networks in embryo-derived pluripotent stem cells. Nat Rev Mol Cell Biol 6:872–884PubMedGoogle Scholar
  12. Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737PubMedGoogle Scholar
  13. Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli MC, degli Uberti EC (2005) miR-15a and miR-16–1 down-regulation in pituitary adenomas. J Cell Physiol 204:280–285PubMedGoogle Scholar
  14. Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122:947–956PubMedGoogle Scholar
  15. Cai X, Lu S, Zhang Z, Gonzalez CM, Damania B, Cullen BR (2005) Kaposi’s sarcoma-associated Herpes virus expresses an array of viral microRNAs in latently infected cells. Proc Natl Acad Sci USA 102:5570–5575PubMedGoogle Scholar
  16. Cao X, Pfaff SL, Gage FH (2007) A functional study of miR-124 in the developing neural tube. Genes Dev 21:531–536PubMedGoogle Scholar
  17. Chen D, McKearin D (2003) Dpp signaling silences Bam transcription directly to establish asymmetric divisions of germline stem cells. Curr Biol 13:1786–1791PubMedGoogle Scholar
  18. Chen D, McKearin D (2005) Gene circuitry controlling a stem cell niche. Curr Biol 15:179–184PubMedGoogle Scholar
  19. Chen CZ, Li L, Lodish HF, Bartel DP (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303:83–86PubMedGoogle Scholar
  20. Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, Conlon FL, Wang DZ (2006) The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 38:228–233PubMedGoogle Scholar
  21. Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 102:13944–13949PubMedGoogle Scholar
  22. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65:10946–10951PubMedGoogle Scholar
  23. Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF (2007) Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA 104:10158–10163PubMedGoogle Scholar
  24. Dalmay T, Hamilton A, Rudd S, Angell S, Baulcombe DC (2000) An RNA-dependent RNA polymerase gene in Arabidopsis is required for posttranscriptional gene silencing mediated by a transgene but not by a virus. Cell 101:543–553PubMedGoogle Scholar
  25. Dews M, Homayouni A, Yu D, Murphy D, Sevignani C, Wentzel E, Furth EE, Lee WM, Enders GH, Mendell JT, Thomas-Tikhonenko A (2006) Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet 38:1060–1065PubMedGoogle Scholar
  26. Donnelly DS, Krause DS (2001) Hematopoietic stem cells can be CD34+ or CD34. Leuk Lymphoma 40:221–234PubMedGoogle Scholar
  27. Eisterer W, Jiang X, Christ O, Glimm H, Lee KH, Pang E, Lambie K, Shaw G, Holyoake TL, Petzer AL, Auewarakul C, Barnett MJ, Eaves CJ, Eaves AC (2005) Different subsets of primary chronic myeloid leukemia stem cells engraft immunodeficient mice and produce a model of the human disease. Leukemia 19:435–441PubMedGoogle Scholar
  28. Elbashir SM, Lendeckel W, Tuschl T (2001) RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev 15:188–200PubMedGoogle Scholar
  29. Fan X, Matsui W, Khaki L, Stearns D, Chun J, Li YM, Eberhart CG (2006) Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors. Cancer Res 66:7445–7452PubMedGoogle Scholar
  30. Fang D, Nguyen TK, Leishear K, Finko R, Kulp AN, Hotz S, Van Belle PA, Xu X, Elder DE, Herlyn M (2005) A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 65:9328–9337PubMedGoogle Scholar
  31. Forstemann K, Horwich MD, Wee L, Tomari Y, Zamore PD (2007) Drosophila microRNAs are sorted into functionally distinct Argonaute complexes after production by Dicer-1. Cell 130:287–297PubMedGoogle Scholar
  32. Fuchs EJ, Whartenby KA (2004) Hematopoietic stem cell transplant as a platform for tumor immunotherapy. Curr Opin Mol Ther 6:48–53PubMedGoogle Scholar
  33. Georgantas RW 3rd, Hildreth R, Morisot S, Alder J, Liu CG, Heimfeld S, Calin GA, Croce CM, Civin CI (2007) CD34+ hematopoietic stem-progenitor cell microRNA expression and function: a circuit diagram of differentiation control. Proc Natl Acad Sci USA 104:2750–2755PubMedGoogle Scholar
  34. Gibbs CP, Kukekov VG, Reith JD, Tchigrinova O, Suslov ON, Scott EW, Ghivizzani SC, Ignatova TN, Steindler DA (2005) Stem-like cells in bone sarcomas: implications for tumorigenesis. Neoplasia 7:967–976PubMedGoogle Scholar
  35. Giraldez AJ, Mishima Y, Rihel J, Grocock RJ, Van Dongen S, Inoue K, Enright AJ, Schier AF (2006) Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science 312:75–79PubMedGoogle Scholar
  36. Goodman JW, Hodgson GS (1962) Evidence for stem cells in the peripheral blood of mice. Blood 19:702–714PubMedGoogle Scholar
  37. Greber B, Lehrach H, Adjaye J (2007) Silencing of core transcription factors in human EC cells highlights the importance of autocrine FGF signaling for self-renewal. BMC Dev Biol 7:46PubMedGoogle Scholar
  38. Grivna ST, Pyhtila B, Lin H (2006) MIWI associates with translational machinery and PIWI-interacting RNAs (piRNAs) in regulating spermatogenesis. Proc Natl Acad Sci USA 103:13415–13420PubMedGoogle Scholar
  39. Gu G, Yuan J, Wills M, Kasper S (2007) Prostate cancer cells with stem cell characteristics reconstitute the original human tumor in vivo. Cancer Res 67:4807–4815PubMedGoogle Scholar
  40. Hammond SM, Bernstein E, Beach D, Hannon GJ (2000) An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 404:293–296PubMedGoogle Scholar
  41. Hammond SM, Boettcher S, Caudy AA, Kobayashi R, Hannon GJ (2001a) Argonaute2, a link between genetic and biochemical analyses of RNAi. Science 293:1146–1150PubMedGoogle Scholar
  42. Hammond SM, Caudy AA, Hannon GJ (2001b) Post-transcriptional gene silencing by double-stranded RNA. Nat Rev Genet 2:110–119PubMedGoogle Scholar
  43. Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN (2004) The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev 18:3016–3027PubMedGoogle Scholar
  44. Hatfield SD, Shcherbata HR, Fischer KA, Nakahara K, Carthew RW, Ruohola-Baker H (2005) Stem cell division is regulated by the microRNA pathway. Nature 435:974–978PubMedGoogle Scholar
  45. Hatfield S, Shcherbata HR, Ward EJ, Reynolds S, Ruohola-Baker H (2007) Clarke N, Sanseau P (eds) MicroRNAs and their involvement in stem cell division, in microRNAs; biology, function and expressionGoogle Scholar
  46. Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, Yatabe Y, Kawahara K, Sekido Y, Takahashi T (2005) A polycistronic microRNA cluster, miR-17–92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 65:9628–9632PubMedGoogle Scholar
  47. He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, Calin GA, Liu CG, Franssila K, Suster S, Kloos RT, Croce CM, de la Chapelle A (2005a) The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA 102:19075–19080PubMedGoogle Scholar
  48. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM (2005b) A microRNA polycistron as a potential human oncogene. Nature 435:828–833PubMedGoogle Scholar
  49. Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U, Goodell MA, Brenner MK (2004) A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA 101:14228–14233PubMedGoogle Scholar
  50. Ho MM, Ng AV, Lam S, Hung JY (2007) Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res 67:4827–4833PubMedGoogle Scholar
  51. Hope KJ, Jin L, Dick JE (2004) Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol 5:738–743PubMedGoogle Scholar
  52. Horwich MD, Li C, Matranga C, Vagin V, Farley G, Wang P, Zamore PD (2007) The Drosophila RNA methyltransferase, DmHen1, modifies germline piRNAs and single-stranded siRNAs in RISC. Curr Biol 17:1265–1272PubMedGoogle Scholar
  53. Hossain A, Kuo MT, Saunders GF (2006) Mir-17–5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA. Mol Cell Biol 26:8191–8201PubMedGoogle Scholar
  54. Houbaviy HB, Murray MF, Sharp PA (2003) Embryonic stem cell-specific microRNAs. Dev Cell 5:351–358PubMedGoogle Scholar
  55. Jin Z, Xie T (2007) Dcr-1 maintains Drosophila ovarian stem cells. Curr Biol 17:539–544PubMedGoogle Scholar
  56. Kanellopoulou C, Muljo SA, Kung AL, Ganesan S, Drapkin R, Jenuwein T, Livingston DM, Rajewsky K (2005) Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev 19:489–501PubMedGoogle Scholar
  57. Keller G, Kennedy M, Papayannopoulou T, Wiles MV (1993) Hematopoietic commitment during embryonic stem cell differentiation in culture. Mol Cell Biol 13:473–486PubMedGoogle Scholar
  58. Kennedy M, Keller GM (2003) Hematopoietic commitment of ES cells in culture. Methods Enzymol 365:39–59PubMedCrossRefGoogle Scholar
  59. Kilpatrick TJ, Bartlett PF (1993) Cloning and growth of multipotential neural precursors: requirements for proliferation and differentiation. Neuron 10:255–265PubMedGoogle Scholar
  60. Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S, Crowley D, Bronson RT, Jacks T (2005) Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121:823–835PubMedGoogle Scholar
  61. Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M (2005) Silencing of microRNAs in vivo with “antagomirs”. Nature 438:685–689PubMedGoogle Scholar
  62. Lai EC (2002) Micro RNAs are complementary to 3′UTR sequence motifs that mediate negative post-transcriptional regulation. Nat Genet 30:363–364PubMedGoogle Scholar
  63. Lau NC, Seto AG, Kim J, Kuramochi-Miyagawa S, Nakano T, Bartel DP, Kingston RE (2006) Characterization of the piRNA complex from rat testes. Science 313:363–367PubMedGoogle Scholar
  64. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854PubMedGoogle Scholar
  65. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Radmark O, Kim S, Kim VN (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature 425:415–419PubMedGoogle Scholar
  66. Lee YS, Nakahara K, Pham JW, Kim K, He Z, Sontheimer EJ, Carthew RW (2004) Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways. Cell 117:69–81PubMedGoogle Scholar
  67. Li CL, Johnson GR (1995) Murine hematopoietic stem and progenitor cells. I. Enrichment and biologic characterization. Blood 85:1472–1479PubMedGoogle Scholar
  68. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM (2007) Identification of pancreatic cancer stem cells. Cancer Res 67:1030–1037PubMedGoogle Scholar
  69. Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ, Hammond SM, Joshua-Tor L, Hannon GJ (2004) Argonaute2 is the catalytic engine of mammalian RNAi. Science 305:1437–1441PubMedGoogle Scholar
  70. Llave C, Xie Z, Kasschau KD, Carrington JC (2002) Cleavage of Scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA. Science 297:2053–2056PubMedGoogle Scholar
  71. Loh YH, Wu Q, Chew JL, Vega VB, Zhang W, Chen X, Bourque G, George J, Leong B, Liu J, Wong KY, Sung KW, Lee CW, Zhao XD, Chiu KP, Lipovich L, Kuznetsov VA, Robson P, Stanton LW, Wei CL, Ruan Y, Lim B, Ng HH (2006) The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 38:431–440PubMedGoogle Scholar
  72. Lujambio A, Ropero S, Ballestar E, Fraga MF, Cerrato C, Setien F, Casado S, Suarez-Gauthier A, Sanchez-Cespedes M, Git A, Spiteri I, Das PP, Caldas C, Miska E, Esteller M (2007) Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res 67:1424–1429PubMedGoogle Scholar
  73. Maines JZ, Park JK, Williams M, McKearin DM (2007) Stonewalling Drosophila stem cell differentiation by epigenetic controls. Development 134:1471–1479PubMedGoogle Scholar
  74. Makeyev EV, Zhang J, Carrasco MA, Maniatis T (2007) The microRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell 27(3):435–448, August 3PubMedGoogle Scholar
  75. Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 78:7634–7638PubMedGoogle Scholar
  76. McKinstry WJ, Li CL, Rasko JE, Nicola NA, Johnson GR, Metcalf D (1997) Cytokine receptor expression on hematopoietic stem and progenitor cells. Blood 89:65–71PubMedGoogle Scholar
  77. Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T (2004) Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 15:185–197PubMedGoogle Scholar
  78. Meshorer E, Yellajoshula D, George E, Scambler PJ, Brown DT, Misteli T (2006) Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Dev Cell 10:105–116PubMedGoogle Scholar
  79. Miyoshi K, Tsukumo H, Nagami T, Siomi H, Siomi MC (2005) Slicer function of Drosophila Argonautes and its involvement in RISC formation. Genes Dev 19:2837–2848PubMedGoogle Scholar
  80. Molnar A, Schwach F, Studholme DJ, Thuenemann EC, Baulcombe DC (2007) miRNAs control gene expression in the single-cell alga Chlamydomonas reinhardtii. Nature 447:1126–1129PubMedGoogle Scholar
  81. Moorthy PP, Kumar AA, Devaraj H (2005) Expression of the Gas7 gene and Oct4 in embryonic stem cells of mice. Stem Cells Dev 14:664–670PubMedGoogle Scholar
  82. Morshead CM, Reynolds BA, Craig CG, McBurney MW, Staines WA, Morassutti D, Weiss S, van der Kooy D (1994) Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells. Neuron 13:1071–1082PubMedGoogle Scholar
  83. Mossman AK, Sourris K, Ng E, Stanley EG, Elefanty AG (2005) Mixl1 and oct4 proteins are transiently co-expressed in differentiating mouse and human embryonic stem cells. Stem Cells Dev 14:656–663PubMedGoogle Scholar
  84. Motamedi MR, Verdel A, Colmenares SU, Gerber SA, Gygi SP, Moazed D (2004) Two RNAi complexes, RITS and RDRC, physically interact and localize to noncoding centromeric RNAs. Cell 119:789–802PubMedGoogle Scholar
  85. Mott JL, Kobayashi S, Bronk SF, Gores GJ (2007) mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene 26:6133–6140PubMedGoogle Scholar
  86. Murchison EP, Partridge JF, Tam OH, Cheloufi S, Hannon GJ (2005) Characterization of Dicer-deficient murine embryonic stem cells. Proc Natl Acad Sci USA 102:12135–12140PubMedGoogle Scholar
  87. Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I, Scholer H, Smith A (1998) Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 95:379–391PubMedGoogle Scholar
  88. Niwa H (2007) How is pluripotency determined and maintained? Development 134:635–646PubMedGoogle Scholar
  89. O’Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445:106–110PubMedGoogle Scholar
  90. Okamura K, Ishizuka A, Siomi H, Siomi MC (2004) Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways. Genes Dev 18:1655–1666PubMedGoogle Scholar
  91. Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448:313–317PubMedGoogle Scholar
  92. Olsen PH, Ambros V (1999) The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol 216:671–680PubMedGoogle Scholar
  93. Pal-Bhadra M, Leibovitch BA, Gandhi SG, Rao M, Bhadra U, Birchler JA, Elgin SC (2004) Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery. Science 303:669–672PubMedGoogle Scholar
  94. Park JK, Liu X, Strauss TJ, McKearin DM, Liu Q (2007) The miRNA pathway intrinsically controls self-renewal of Drosophila germline stem cells. Curr Biol 17:533–538PubMedGoogle Scholar
  95. Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, Reilly JG, Chandra D, Zhou J, Claypool K, Coghlan L, Tang DG (2006) Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 25:1696–1708PubMedGoogle Scholar
  96. Phillips RL, Ernst RE, Brunk B, Ivanova N, Mahan MA, Deanehan JK, Moore KA, Overton GC, Lemischka IR (2000) The genetic program of hematopoietic stem cells. Science 288:1635–1640PubMedGoogle Scholar
  97. Politz JC, Zhang F, Pederson T (2006) MicroRNA-206 colocalizes with ribosome-rich regions in both the nucleolus and cytoplasm of rat myogenic cells. Proc Natl Acad Sci USA 103:18957–18962PubMedGoogle Scholar
  98. Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE (2007) Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA 104:973–978PubMedGoogle Scholar
  99. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445:111–115PubMedGoogle Scholar
  100. Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A (2004) Identification of mammalian microRNA host genes and transcription units. Genome Res 14:1902–1910PubMedGoogle Scholar
  101. Ruby JG, Jan CH, Bartel DP (2007) Intronic microRNA precursors that bypass Drosha processing. Nature 448:83–86PubMedGoogle Scholar
  102. Saito K, Sakaguchi Y, Suzuki T, Suzuki T, Siomi H, Siomi MC (2007) Pimet, the Drosophila homolog of HEN1, mediates 2′-O-methylation of Piwi- interacting RNAs at their 3′ ends. Genes Dev 21:1603–1608PubMedGoogle Scholar
  103. Sevignani C, Calin GA, Nnadi SC, Shimizu M, Davuluri RV, Hyslop T, Demant P, Croce CM, Siracusa LD (2007) MicroRNA genes are frequently located near mouse cancer susceptibility loci. Proc Natl Acad Sci USA 104:8017–8022PubMedGoogle Scholar
  104. Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY (2007) miR-21-mediated tumor growth. Oncogene 26:2799–2803PubMedGoogle Scholar
  105. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401PubMedGoogle Scholar
  106. Sitnicka E, Buza-Vidas N, Larsson S, Nygren JM, Liuba K, Jacobsen SE (2003) Human CD34+ hematopoietic stem cells capable of multilineage engrafting NOD/SCID mice express flt3: distinct flt3 and c-kit expression and response patterns on mouse and candidate human hematopoietic stem cells. Blood 102:881–886PubMedGoogle Scholar
  107. Slack FJ, Basson M, Liu Z, Ambros V, Horvitz HR, Ruvkun G (2000) The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Mol Cell 5:659–669PubMedGoogle Scholar
  108. Smardon A, Spoerke JM, Stacey SC, Klein ME, Mackin N, Maine EM (2000) EGO-1 is related to RNA-directed RNA polymerase and functions in germ-line development and RNA interference in C. elegans. Curr Biol 10:169–178PubMedGoogle Scholar
  109. Song JJ, Smith SK, Hannon GJ, Joshua-Tor L (2004a) Crystal structure of Argonaute and its implications for RISC slicer activity. Science 305:1434–1437PubMedGoogle Scholar
  110. Song X, Wong MD, Kawase E, Xi R, Ding BC, McCarthy JJ, Xie T (2004b) Bmp signals from niche cells directly repress transcription of a differentiation-promoting gene, bag of marbles, in germline stem cells in the Drosophila ovary. Development 131:1353–1364PubMedGoogle Scholar
  111. Song X, Call GB, Kirilly D, Xie T (2007) Notch signaling controls germline stem cell niche formation in the Drosophila ovary. Development 134:1071–1080PubMedGoogle Scholar
  112. Suh MR, Lee Y, Kim JY, Kim SK, Moon SH, Lee JY, Cha KY, Chung HM, Yoon HS, Moon SY, Kim VN, Kim KS (2004) Human embryonic stem cells express a unique set of microRNAs. Dev Biol 270:488–498PubMedGoogle Scholar
  113. Szakmary A, Cox DN, Wang Z, Lin H (2005) Regulatory relationship among piwi, pumilio, and bag-of-marbles in Drosophila germline stem cell self-renewal and differentiation. Curr Biol 15:171–178PubMedGoogle Scholar
  114. Tai MH, Chang CC, Kiupel M, Webster JD, Olson LK, Trosko JE (2005) Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis 26:495–502PubMedGoogle Scholar
  115. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676PubMedGoogle Scholar
  116. Tang C, Ang BT, Pervaiz S (2007) Cancer stem cell: target for anti-cancer therapy. FASEB J (in press)Google Scholar
  117. Tran N, McLean T, Zhang X, Zhao CJ, Thomson JM, O’Brien C, Rose B (2007) MicroRNA expression profiles in head and neck cancer cell lines. Biochem Biophys Res Commun 358:12–17PubMedGoogle Scholar
  118. Vagin VV, Sigova A, Li C, Seitz H, Gvozdev V, Zamore PD (2006) A distinct small RNA pathway silences selfish genetic elements in the germline. Science 313:320–324PubMedGoogle Scholar
  119. Velkey JM, O’Shea KS (2003) Oct4 RNA interference induces trophectoderm differentiation in mouse embryonic stem cells. Genesis 37:18–24PubMedGoogle Scholar
  120. Verdel A, Jia S, Gerber S, Sugiyama T, Gygi S, Grewal SI, Moazed D (2004) RNAi-mediated targeting of heterochromatin by the RITS complex. Science 303:672–676PubMedGoogle Scholar
  121. Visvanathan J, Lee S, Lee B, Lee JW, Lee SK (2007) The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development. Genes Dev 21(7):744–749, April 1PubMedGoogle Scholar
  122. Voorhoeve PM, le Sage C, Schrier M, Gillis AJ, Stoop H, Nagel R, Liu YP, van Duijse J, Drost J, Griekspoor A, Zlotorynski E, Yabuta N, De Vita G, Nojima H, Looijenga LH, Agami R (2006) A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell 124:1169–1181PubMedGoogle Scholar
  123. Wakiyama M, Takimoto K, Ohara O, Yokoyama S (2007) Let-7 microRNA-mediated mRNA deadenylation and translational repression in a mammalian cell-free system. Genes Dev 21:1857–1862PubMedGoogle Scholar
  124. Wang L, Li L, Menendez P, Cerdan C, Bhatia M (2005) Human embryonic stem cells maintained in the absence of mouse embryonic fibroblasts or conditioned media are capable of hematopoietic development. Blood 105:4598–4603PubMedGoogle Scholar
  125. Wang J, Guo LP, Chen LZ, Zeng YX, Lu SH (2007) Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line. Cancer Res 67:3716–3724PubMedGoogle Scholar
  126. Ward EJ, Shcherbata HR, Reynolds SH, Fischer KA, Hatfield SD, Ruohola-Baker H (2006) Stem cells signal to the niche through the Notch pathway in the Drosophila ovary. Curr Biol 16:2352–2358PubMedGoogle Scholar
  127. Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE, Jaenisch R (2007) In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448:318–324PubMedGoogle Scholar
  128. Wiles MV, Keller G (1991) Multiple hematopoietic lineages develop from embryonic stem (ES) cells in culture. Development 111:259–267PubMedGoogle Scholar
  129. Williams BP, Read J, Price J (1991) The generation of neurons and oligodendrocytes from a common precursor cell. Neuron 7:685–693PubMedGoogle Scholar
  130. Wulczyn FG, Smirnova L, Rybak A, Brandt C, Kwidzinski E, Ninnemann O, Strehle M, Seiler A, Schumacher S, Nitsch R (2007) Post-transcriptional regulation of the let-7 microRNA during neural cell specification. FASEB J 21:415–426PubMedGoogle Scholar
  131. Xi R, Xie T (2005) Stem cell self-renewal controlled by chromatin remodeling factors. Science 310:1487–1489PubMedGoogle Scholar
  132. Yang Z, Ebright YW, Yu B, Chen X (2006) HEN1 recognizes 21–24 nt small RNA duplexes and deposits a methyl group onto the 2′ OH of the 3′ terminal nucleotide. Nucleic Acids Res 34:667–675PubMedGoogle Scholar
  133. Yekta S, Shih IH, Bartel DP (2004) MicroRNA-directed cleavage of HOXB8 mRNA. Science 304:594–596PubMedGoogle Scholar
  134. Yuan X, Curtin J, Xiong Y, Liu G, Waschsmann-Hogiu S, Farkas DL, Black KL, Yu JS (2004) Isolation of cancer stem cells from adult glioblastoma multiforme. Oncogene 23:9392–9400PubMedGoogle Scholar
  135. Zhao L, Kim Y, Dinh TT, Chen X (2007a) miR172 regulates stem cell fate and defines the inner boundary of APETALA3 and PISTILLATA expression domain in Arabidopsis floral meristems. Plant J 51:840–849Google Scholar
  136. Zhao T, Li G, Mi S, Li S, Hannon GJ, Wang XJ, Qi Y (2007b) A complex system of small RNAs in the unicellular green alga Chlamydomonas reinhardtii. Genes Dev 21:1190–1203PubMedGoogle Scholar
  137. Zheng X, Shen G, Yang X, Liu W (2007) Most C6 cells are cancer stem cells: evidence from clonal and population analyses. Cancer Res 67:3691–3697PubMedGoogle Scholar
  138. Zhu S, Si ML, Wu H, Mo YY (2007) MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 282:14328–14336PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Department of Biochemistry, Institute for Stem Cell and Regenerative MedicineUniversity of WashingtonSeattleUSA

Personalised recommendations