Skip to main content
SpringerLink
Log in

MicroRNAs in Development, Stem Cell Differentiation, and Regenerative Medicine

  • Chapter
  • First Online:
Regulatory RNAs

  • 1659 Accesses

Abstract

Mammalian development and cellular differentiation are robust but tightly controlled processes. MicroRNAs have emerged as key players in posttranscriptional regulation of gene expression during development and cellular differentiation. As analytical tools advance from cloning techniques to microarrays and most recently to massively parallel deep sequencing technologies, the space of known microRNAs and their target mRNAs is better defined and is leading to a comprehensive catalog combined with functional characterization. Several tissue- and cell-lineage-specific microRNAs have been identified, some of which are associated with distinct stages of cell identity from stem to progenitor to terminally differentiated cells. We describe the important functional roles of some of these microRNAs as exemplified by the ability of their exogenous expression to elicit changes in cell fate and discuss how, with this knowledge, we can dispense with genetic manipulation and begin to harness the advantage of microRNAs, microRNA mimics, microRNA antagonists (antagomirs), antisense RNA, siRNA, and alike molecules as tools for regenerative medicine and therapy.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AML:

Acute myeloid leukemia

AS (C):

Adipose tissue–derived stem (cell)

asRNA:

Antisense RNA

BP:

B-cell progenitor

C. elegans :

Caenorhabditis elegans

CLP:

Common lymphoid progenitor

CMP:

Common myeloid progenitor

CMV:

Cytomegalovirus

Cre:

Causes recombination

Dgcr8:

DiGeorge syndrome critical region gene 8

DNA:

Deoxyribonucleic acid

E:

Embryonic (stage/day postconception)

EB:

Embryoid body

EC:

Embryo(nic) carcinoma

EMT:

Epithelial-mesenchymal transition

ES:

Embryonic stem

GFP:

Green fluorescent protein

GMP:

Granulocyte macrophage progenitor

h:

Human

HIV:

Human immunodeficiency virus

HSC:

Hematopoietic stem cell

ICM:

Inner cell mass

iPS(C):

Induced pluripotent stem (cell)

lacZ:

Gene encoding bacterial β-galactosidase

LNA:

Locked nucleic acid

loxP:

Locus of chromosomal crossover in the bacteriophage P1

LV:

Lentivirus

m:

Mouse

MEP:

Megakaryocyte erythrocyte progenitor

miR:

MicroRNA

miRISC:

MicroRNA-induced silencing complex

MPP:

Multipotent progenitor

ncRNA:

Noncoding RNA

NK:

Natural killer (cell)

NKP:

NK cell progenitor

NSC:

Neural stem cell

P:

Postnatal (day)

PCR:

Polymerase chain reaction

RA:

Retinoic acid

RCME:

Recombination-mediated cassette exchange

RNA:

Ribonucleic acid

shRNA:

Short hairpin RNA

siRNA:

Small interfering RNA

SNALP:

Stable nucleic-acid-lipid particles

SRF:

Serum response factor

Th:

T helper type

TK:

Thymidine kinase

TP:

T-cell progenitor

TSS:

Transcription/transcript start site

UTR:

Untranslated region

References

  • Ambasudhan R, Talantova M, Coleman R, Yuan X, Zhu S, Lipton S, Ding S (2011) Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions. Cell Stem Cell 9(2):113–118. doi:10.1016/j.stem.2011.07.002

    PubMed  CAS  Google Scholar 

  • Anderson C, Catoe H, Werner R (2006) MIR-206 regulates connexin43 expression during skeletal muscle development. Nucleic Acids Res 34(20):5863–5871. doi:10.1093/nar/gkl743

    PubMed  CAS  Google Scholar 

  • Anokye-Danso F, Trivedi CM, Juhr D, Gupta M, Cui Z, Tian Y, Zhang Y, Yang W, Gruber PJ, Epstein JA, Morrisey EE (2011) Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell 8(4):376–388. doi:10.1073/pnas.0506216102

    PubMed  CAS  Google Scholar 

  • Aranha MM, Santos DM, Sola S, Steer CJ, Rodrigues CM (2011) miR-34a regulates mouse neural stem cell differentiation. PLoS One 6(8):e21396. doi:10.1371/journal.pone.0021396

    PubMed  CAS  Google Scholar 

  • Baroukh N, Ravier MA, Loder MK, Hill EV, Bounacer A, Scharfmann R, Rutter GA, Van Obberghen E (2007) MicroRNA-124a regulates Foxa2 expression and intracellular signaling in pancreatic – cell lines. J Biol Chem 282(27):19575–19588. doi:10.1074/jbc.M611841200

    PubMed  CAS  Google Scholar 

  • 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(3):215–217. doi:10.1038/ng1253

    PubMed  CAS  Google Scholar 

  • Bracken CP, Gregory PA, Khew-Goodall Y, Goodall GJ (2009) The role of microRNAs in metastasis and epithelial-mesenchymal transition. Cell Mol Life Sci 66(10):1682–1699. doi:10.1007/s00018-009-8750-1

    PubMed  CAS  Google Scholar 

  • Brown BD, Naldini L (2009) Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications. Nat Rev Genet 10(8):578–585. doi:10.1038/nrg2628

    PubMed  CAS  Google Scholar 

  • Brown BD, Gentner B, Cantore A, Colleoni S, Amendola M, Zingale A, Alessia B, Lazzari G, Galli C, Naldini L (2007) Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state. Nat Biotechnol 25(12):1457–1467. doi:10.1038/nbt1372

    PubMed  CAS  Google Scholar 

  • Burnett JC, Rossi JJ, Tiemann K (2011) Current progress of siRNA/shRNA therapeutics in clinical trials. Biotechnol J. doi:10.1002/biot.201100054

    Google Scholar 

  • Callis TE, Deng Z, Chen JF, Wang DZ (2008) Muscling through the microRNA world. Exp Biol Med 233(2):131–138. doi:10.3181/0709-mr-237

    CAS  Google Scholar 

  • Carvajal-Vergara X, Sevilla A, D’Souza SL, Ang Y-S, Schaniel C, Lee D-F, Yang L, Kaplan AD, Adler ED, Rozov R, Ge Y, Cohen N, Edelmann LJ, Chang B, Waghray A, Su J, Pardo S, Lichtenbelt KD, Tartaglia M, Gelb BD, Lemischka IR (2010) Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature 465(7299):808–812. doi:10.1038/nature09005

    PubMed  CAS  Google Scholar 

  • Chen CZ (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303(5654):83–86. doi:10.1126/science.1091903

    PubMed  CAS  Google Scholar 

  • Chen J-F, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, Conlon FL, Wang D-Z (2005) The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 38(2):228–233. doi:10.1038/ng1725

    PubMed  Google Scholar 

  • Chen C, Ridzon D, Lee C-T, Blake J, Sun Y, Strauss WM (2007) Defining embryonic stem cell identity using differentiation-related microRNAs and their potential targets. Mamm Genome 18(5):316–327. doi:10.1007/s00335-007-9032-6

    PubMed  CAS  Google Scholar 

  • Chen JF, Tao Y, Li J, Deng Z, Yan Z, Xiao X, Wang DZ (2010) microRNA-1 and microRNA-206 regulate skeletal muscle satellite cell proliferation and differentiation by repressing Pax7. J Cell Biol 190(5):867–879. doi:10.1083/jcb.200911036

    PubMed  CAS  Google Scholar 

  • Chi SW, Zang JB, Mele A, Darnell RB (2009) Argonaute HITS-CLIP decodes microRNA–mRNA interaction maps. Nature. doi:10.1038/nature08170

    Google Scholar 

  • Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, Lee T-H, Miano JM, Ivey KN, Srivastava D (2009) miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature. doi:10.1038/nature08195

    Google Scholar 

  • Czech MP, Aouadi M, Tesz GJ (2011) RNAi-based therapeutic strategies for metabolic disease. Nat Rev Endocrinol 7(8):473–484. doi:10.1038/nrendo.2011.57

    PubMed  CAS  Google Scholar 

  • Davidson BL, McCray PB Jr (2011) Current prospects for RNA interference-based therapies. Nat Rev Genet 12(5):329–340. doi:10.1038/nrg2968

    PubMed  CAS  Google Scholar 

  • Davis ME, Zuckerman JE, Choi CH, Seligson D, Tolcher A, Alabi CA, Yen Y, Heidel JD, Ribas A (2010) Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 464(7291):1067–1070. doi:10.1038/nature08956

    PubMed  CAS  Google Scholar 

  • DiGiusto DL, Krishnan A, Li L, Li H, Li S, Rao A, Mi S, Yam P, Stinson S, Kalos M, Alvarnas J, Lacey SF, Yee JK, Li M, Couture L, Hsu D, Forman SJ, Rossi JJ, Zaia JA (2010) RNA-based gene therapy for HIV with lentiviral vector-modified CD34(+) cells in patients undergoing transplantation for AIDS-related lymphoma. Sci Transl Med 2(36):36–43. doi:10.1126/scitranslmed.3000931

    Google Scholar 

  • Ebert MS, Neilson JR, Sharp PA (2007) MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 4(9):721–726. doi:10.1038/nmeth1079

    PubMed  CAS  Google Scholar 

  • Esau C, Kang X, Peralta E, Hanson E, Marcusson EG, Ravichandran LV, Sun Y, Koo S, Perera RJ, Jain R, Dean NM, Freier SM, Bennett CF, Lollo B, Griffey R (2004) MicroRNA-143 regulates adipocyte differentiation. J Biol Chem 279(50):52361–52365. doi:10.1074/jbc.C400438200

    PubMed  CAS  Google Scholar 

  • Evans M, Kaufman M (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292(5819):154–156. doi:10.1038/292154a0

    PubMed  CAS  Google Scholar 

  • Felli N (2005) MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci 102(50):18081–18086. doi:10.1073/pnas.0506216102

    PubMed  CAS  Google Scholar 

  • Felli N, Pedini F, Romania P, Biffoni M, Morsilli O, Castelli G, Santoro S, Chicarella S, Sorrentino A, Peschle C, Marziali G (2009) MicroRNA 223-dependent expression of LMO2 regulates normal erythropoiesis. Haematologica 94(4):479–486. doi:10.3324/haematol.2008.002345

    PubMed  CAS  Google Scholar 

  • Georgantas RW, Hildreth R, Morisot S, Alder J, Liu C-G, 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 104(8):2750–2755. doi:10.1073/pnas.0610983104

    PubMed  CAS  Google Scholar 

  • Giraldez AJ, Cinalli RM, Glasner ME, Enright AJ, Thomson JM, Baskerville S, Hammond SM, Bartel DP, Schier AF (2005) MicroRNAs regulate brain morphogenesis in zebrafish. Science 308(5723):833–838. doi:10.1016/j.gde.2010.04.003

    PubMed  CAS  Google Scholar 

  • Glass C, Singla DK (2011) microRNA-1 transfected embryonic stem cells enhance cardiac myocyte differentiation and inhibit apoptosis by modulating PTEN/Akt pathway in the infarcted heart. Am J Physiol Heart Circ Physiol. doi:10.1152/ajpheart.00271.2011

    Google Scholar 

  • Großhans H, Johnson T, Reinert KL, Gerstein M, Slack FJ (2005) The temporal patterning microRNA let-7 regulates several transcription factors at the larval to adult transition in C. elegans. Dev Cell 8(3):321–330. doi:10.1016/j.devcel.2004.12.019

    PubMed  Google Scholar 

  • Hafner M, Landthaler M, Burger L, Khorshid M, Hausser J, Berninger P, Rothballer A, Ascano M, Jungkamp A-C, Munschauer M, Ulrich A, Wardle GS, Dewell S, Zavolan M, Tuschl T (2010) Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141(1):129–141. doi:10.1016/j.cell.2010.03.009

    PubMed  CAS  Google Scholar 

  • Harfe BD (2005a) MicroRNAs in vertebrate development. Curr Opin Genet Dev 15(4):410–415. doi:10.1016/j.gde.2005.06.012

    PubMed  CAS  Google Scholar 

  • Harfe BD (2005b) The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc Natl Acad Sci 102(31):10898–10903. doi:10.1073/pnas.0504834102

    PubMed  CAS  Google Scholar 

  • Hino K, Fukao T, Watanabe M (2007) Regulatory interaction of HNF1 to microRNA194 gene during intestinal epithelial cell differentiation. Nucleic Acids Symp Ser 51(1):415–416. doi:10.1093/nass/nrm208

    Google Scholar 

  • Hino K, Tsuchiya K, Fukao T, Kiga K, Okamoto R, Kanai T, Watanabe M (2008) Inducible expression of microRNA-194 is regulated by HNF-1 during intestinal epithelial cell differentiation. RNA 14(7):1433–1442. doi:10.1261/rna.810208

    PubMed  CAS  Google Scholar 

  • Houbaviy HB, Murray MF, Sharp PA (2003) Embryonic stem cell-specific microRNAs. Dev Cell 5(2):351–358. doi:10.1016/s1534-5807(03), 00227-2

    PubMed  CAS  Google Scholar 

  • Huang J, Zhao L, Xing L, Chen D (2010) MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells 28(2):357–364. doi:10.1002/stem.288

    PubMed  Google Scholar 

  • Itoh T, Nozawa Y, Akao Y (2009) MicroRNA-141 and -200a are involved in bone morphogenetic protein-2-induced mouse pre-osteoblast differentiation by targeting distal-less homeobox 5. J Biol Chem 284(29):19272–19279. doi:10.1074/jbc.M109.014001

    PubMed  CAS  Google Scholar 

  • Ivey KN, Srivastava D (2010) MicroRNAs as regulators of differentiation and cell fate decisions. Cell Stem Cell 7(1):36–41. doi:10.1016/j.stem.2010.06.012

    PubMed  CAS  Google Scholar 

  • Ivey KN, Muth A, Arnold J, King FW, Yeh R-F, Fish JE, Hsiao EC, Schwartz RJ, Conklin BR, Bernstein HS, Srivastava D (2008) MicroRNA regulation of cell lineages in mouse and human embryonic stem cells. Cell Stem Cell 2(3):219–229. doi:10.1016/j.stem.2008.01.016

    PubMed  CAS  Google Scholar 

  • Joglekar M, Joglekar V, Hardikar A (2009) Expression of islet-specific microRNAs during human pancreatic development. Gene Expr Patterns 9(2):109–113. doi:10.1016/j.gep. 2008.10.001

    PubMed  CAS  Google Scholar 

  • Judson RL, Babiarz JE, Venere M, Blelloch R (2009) Embryonic stem cell–specific microRNAs promote induced pluripotency. Nat Biotechnol 27(5):459–461. doi:10.1038/nbt.1535

    PubMed  CAS  Google Scholar 

  • Kajimoto K (2006) MicroRNA and 3T3-L1 pre-adipocyte differentiation. RNA 12(9):1626–1632. doi:10.1261/rna.7228806

    PubMed  CAS  Google Scholar 

  • Kanellopoulou C (2005) Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev 19(4):489–501. doi:10.1101/gad.1248505

    PubMed  CAS  Google Scholar 

  • Kapsimali M, Kloosterman WP, de Bruijn E, Rosa F, Plasterk RHA, Wilson SW (2007) MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system. Genome Biol 8(8):R173. doi:10.1186/gb-2007-8-8-r173

    PubMed  Google Scholar 

  • Kawasaki H, Taira K (2004) MicroRNA-196 inhibits HOXB8 expression in myeloid differentiation of HL60 cells. Nucleic Acids Symp Ser 48:211–212. doi:10.1093/nass/48.1

    Google Scholar 

  • Kim HK (2006) Muscle-specific microRNA miR-206 promotes muscle differentiation. J Cell Biol 174(5):677–687. doi:10.1083/jcb.200603008

    PubMed  CAS  Google Scholar 

  • Kim YJ, Bae SW, Yu SS, Bae YC, Jung JS (2009) miR-196a regulates proliferation and osteogenic differentiation in mesenchymal stem cells derived from human adipose tissue. J Bone Miner Res 24(5):816–825. doi:10.1359/jbmr.081230

    PubMed  CAS  Google Scholar 

  • Knowling S, Morris KV (2011) Non-coding RNA. and antisense RNA Nature’s trash or treasure? Biochimie. doi:10.1016/j.biochi.2011.07.031

    Google Scholar 

  • Krichevsky AM, Sonntag KC, Isacson O, Kosik KS (2006) Specific microRNAs modulate embryonic stem cell-derived neurogenesis. Stem Cells 24(4):857–864. doi:10.1634/stemcells.2005-0441

    PubMed  CAS  Google Scholar 

  • Krumlauf R (1994) Hox genes in vertebrate development. Cell 78(2):191–201. doi:10.1016/0092-8674(94), 90290-9

    PubMed  CAS  Google Scholar 

  • Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T (2002) Identification of tissue-specific microRNAs from mouse. Curr Biol 12(9):735–739. doi:10.1016/S0960-9822(02), 00809-6

    PubMed  CAS  Google Scholar 

  • Landthaler M, Gaidatzis D, Rothballer A, Chen PY, Soll SJ, Dinic L, Ojo T, Hafner M, Zavolan M, Tuschl T (2008) Molecular characterization of human Argonaute-containing ribonucleoprotein complexes and their bound target mRNAs. RNA 14(12):2580–2596. doi:10.1261/rna.1351608

    PubMed  CAS  Google Scholar 

  • Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME, Kauppinen S, Orum H (2010) Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327(5962):198–201. doi:10.1126/science.1178178

    PubMed  CAS  Google Scholar 

  • Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854. doi:10.1016/0092-8674(93)90529-Y

    PubMed  CAS  Google Scholar 

  • Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB (2003) Prediction of mammalian microRNA targets. Cell 115(7):787–798. doi:10.1016/S0092-8674(03), 01018-3

    PubMed  CAS  Google Scholar 

  • Liao R, Sun J, Zhang L, Lou G, Chen M, Zhou D, Chen Z, Zhang S (2008) MicroRNAs play a role in the development of human hematopoietic stem cells. J Cell Biochem 104(3):805–817. doi:10.1002/jcb.21668

    PubMed  CAS  Google Scholar 

  • Lim LP, Lau NC, Garrett-Engle P, Grimson A, Schetter JM, Castle J, Bartel DP, Linsley PS, Johnson JM (2005) Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433(7027):769–773. doi:10.1038/nature03315

    PubMed  CAS  Google Scholar 

  • Liu N, Williams AH, Kim Y, McAnally J, Bezprozvannaya S, Sutherland LB, Richardson JA, Bassel-Duby R, Olson EN (2007) An intragenic MEF2-dependent enhancer directs muscle-specific expression of microRNAs 1 and 133. Proc Natl Acad Sci 104(52):20844–20849. doi:10.1073/pnas.0710558105

    PubMed  CAS  Google Scholar 

  • Liu S-P, Fu R-H, Yu H-H, Li K-W, Tsai C-H, Shyu W-C, Lin S-Z (2009) MicroRNAs regulation modulated self-renewal and lineage differentiation of stem cells. Cell Transplant 18(9):1039–1045. doi:10.3727/096368909x471224

    PubMed  Google Scholar 

  • Lu J, Guo S, Ebert BL, Zhang H, Peng X, Bosco J, Pretz J, Schlanger R, Wang JY, Mak RH (2008) MicroRNA-mediated control of cell fate in megakaryocyte-erythrocyte progenitors. Dev Cell 14(6):843–853. doi:10.1016/j.devcel.2008.03.012

    PubMed  CAS  Google Scholar 

  • Luzi E, Marini F, Sala SC, Tognarini I, Galli G, Brandi ML (2007) Osteogenic differentiation of human adipose tissue-derived stem cells is modulated by the miR-26a targeting of the SMAD1 transcription factor. J Bone Miner Res 23(2):287–295. doi:10.1359/jbmr.071011

    Google Scholar 

  • 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. doi:10.1016/j.molcel.2007.07.015

    PubMed  CAS  Google Scholar 

  • Mallanna SK, Rizzino A (2010) Emerging roles of microRNAs in the control of embryonic stem cells and the generation of induced pluripotent stem cells. Dev Biol 344(1):16–25. doi:10.1016/j.ydbio.2010.05.014

    PubMed  CAS  Google Scholar 

  • Mansfield JH, Harfe BD, Nissen R, Obenauer J, Srineel J, Chaudhuri A, Farzan-Kashani R, Zuker M, Pasquinelli AE, Ruvkun G, Sharp PA, Tabin CJ, McManus MT (2004) MicroRNA-responsive ‘sensor’ transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression. Nat Genet 36(10):1079–1083. doi:10.1038/ng1421

    PubMed  CAS  Google Scholar 

  • Marson A, Levine SS, Cole MF, Frampton GM, Brambrink T, Johnstone S, Guenther MG, Johnston WK, Wernig M, Newman J, Calabrese JM, Dennis LM, Volkert TL, Gupta S, Love J, Hannett N, Sharp PA, Bartel DP, Jaenisch R, Young RA (2008) Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell 134(3):521–533. doi:10.1016/j.cell.2008.07.020

    PubMed  CAS  Google Scholar 

  • Martin G (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci 78(12):7634–7638. doi:10.1073/pnas.78.12.7634

    PubMed  CAS  Google Scholar 

  • Masaki S, Ohtsuka R, Abe Y, Muta K, Umemura T (2007) Expression patterns of microRNAs 155 and 451 during normal human erythropoiesis. Biochem Biophys Res Commun 364(3):509–514. doi:10.1016/j.bbrc.2007.10.077

    PubMed  CAS  Google Scholar 

  • Monticelli S, Ansel KM, Xiao C, Socci ND, Krichevsky AM, Thai T-H, Rajewsky N, Marks DS, Sander C, Rajewsky K, Rao A, Kosik KS (2005) MicroRNA profiling of the murine hematopoietic system. Genome Biol 6(8):R71. doi:10.1186/gb-2005-6-8-r71

    PubMed  Google Scholar 

  • Morrissey DV, Lockridge JA, Shaw L, Blanchard K, Jensen K, Breen W, Hartsough K, Machemer L, Radka S, Jadhav V, Vaish N, Zinnen S, Vargeese C, Bowman K, Shaffer CS, Jeffs LB, Judge A, MacLachlan I, Polisky B (2005) Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat Biotechnol 23(8):1002–1007. doi:10.1038/nbt1122

    PubMed  CAS  Google Scholar 

  • Murchison EP (2005) Characterization of Dicer-deficient murine embryonic stem cells. Proc Natl Acad Sci 102(34):12135–12140. doi:10.1073/pnas.0505479102

    PubMed  CAS  Google Scholar 

  • Naguibneva I, Ameyar-Zazoua M, Polesskaya A, Ait-Si-Ali S, Groisman R, Souidi M, Cuvellier S, Harel-Bellan A et al (2006) The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation. Nat Cell Biol 8(3):278–284. doi:10.1038/ncb1373

    PubMed  CAS  Google Scholar 

  • Nakajima N, Takahashi T, Kitamura R, Isodono K, Asada S, Ueyama T, Matsubara H, Oh H (2006) MicroRNA-1 facilitates skeletal myogenic differentiation without affecting osteoblastic and adipogenic differentiation. Biochem Biophys Res Commun 350(4):1006–1012. doi:10.1016/j.bbrc.2006.09.153

    PubMed  CAS  Google Scholar 

  • Nakamura Y, Inloes JB, Katagiri T, Kobayashi T (2011) Chondrocyte-specific microRNA-140 regulates endochondral bone development and targets Dnpep to modulate bone morphogenetic protein signaling. Mol Cell Biol 31(14):3019–3028. doi:10.1128/mcb.05178-11

    PubMed  CAS  Google Scholar 

  • Noguchi S, Mori T, Hoshino Y, Maruo K, Yamada N, Kitade Y, Naoe T, Akao Y (2011) MicroRNA-143 functions as a tumor suppressor in human bladder cancer T24 cells. Cancer Lett 307(2):211–220. doi:10.1016/j.canlet.2011.04.005

    PubMed  CAS  Google Scholar 

  • O’Connell RM, Chaudhuri AA, Rao DS, Gibson WSJ, Balazs AB, Baltimore D (2010) MicroRNAs enriched in hematopoietic stem cells differentially regulate long-term hematopoietic output. Proc Natl Acad Sci 107(32):14235–14240. doi:10.1073/pnas.1009798107

    PubMed  Google Scholar 

  • Ooi AGL, Sahoo D, Adorno M, Wang Y, Weissman IL, Park CY (2010) MicroRNA-125b expands hematopoietic stem cells and enriches for the lymphoid-balanced and lymphoid-biased subsets. Proc Natl Acad Sci 107(50):21505–21510. doi:10.1073/pnas.1016218107

    PubMed  CAS  Google Scholar 

  • Pedersen IM, Cheng G, Wieland S, Volinia S, Croce CM, Chisari FV, David M (2007) Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 449(7164):919–922. doi:10.1038/nature06205

    PubMed  CAS  Google Scholar 

  • Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, MacDonald PE, Pfeffer S, Tuschl T, Rajewsky N, Rorsman P, Stoffel M (2004) A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432(7014):226–230. doi:10.1038/nature03076

    PubMed  CAS  Google Scholar 

  • Prosser HM, Koike-Yusa H, Cooper JD, Law FC, Bradley A (2011) A resource of vectors and ES cells for targeted deletion of microRNAs in mice. Nat Biotechnol. doi:10.1038/nbt.1929

    Google Scholar 

  • Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Fougvie AE, Horvitz HR, Ruvkun G (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403(6772):901–906. doi:10.1038/35002607

    PubMed  CAS  Google Scholar 

  • Rogler CE, LeVoci L, Ader T, Massimi A, Tchaikovskaya T, Norel R, Rogler LE (2009) MicroRNA-23b cluster microRNAs regulate transforming growth factor-beta/bone morphogenetic protein signaling and liver stem cell differentiation by targeting Smads. Hepatology 50(2):575–584. doi:10.1002/hep. 22982

    PubMed  CAS  Google Scholar 

  • Romania P, Lulli V, Pelosi E, Biffoni M, Peschle C, Marziali G (2008) MicroRNA 155 modulates megakaryopoiesis at progenitor and precursor level by targeting Ets-1 and Meis1 transcription factors. Br J Haematol. doi:10.1111/j.1365-2141.2008.07382.x

    Google Scholar 

  • Rosa A, Ballarino M, Sorrentino A, Sthandier O, De Angelis FG, Marchioni M, Masella B, Guarini A, Fatica A, Peschle C, Bozzoni I (2007) The interplay between the master transcription factor PU1 and miR-424 regulates human monocyte/macrophage differentiation. Proc Natl Acad Sci 104(50):19849–19854. doi:10.1073/pnas.0706963104

    PubMed  CAS  Google Scholar 

  • Rosenberg MI, Georges SA, Asawachaicharn A, Analau E, Tapscott SJ (2006) MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206. J Cell Biol 175(1):77–85. doi:10.1083/jcb.200603039

    PubMed  CAS  Google Scholar 

  • Rougvie AE (2001) Control of developmental timing in animals. Nature Rev Genet 2(9):690–701. doi:10.1038/35088566

    PubMed  CAS  Google Scholar 

  • Schoolmeesters A, Eklund T, Leake D, Vermeulen A, Smith Q, Aldred SF, Federov Y (2009) Functional profiling reveals critical role for miRNA in differentiation of human mesenchymal stem cells. PLoS One 4(5):e5605. doi:10.1371/journal.pone.0005605

    PubMed  Google Scholar 

  • Sempere LF, Freemantle S, Pitha-Rowe I, Moss EG, Dmitrovsky E, Ambros V (2004) Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol 5(3):R13. doi:10.1186/gb-2004-5-3-r13

    PubMed  Google Scholar 

  • Sheehy NT, Cordes KR, White MP, Ivey KN, Srivastava D (2010) The neural crest-enriched microRNA miR-452 regulates epithelial-mesenchymal signaling in the first pharyngeal arch. Development 137(24):4307–4316. doi:10.1242/dev.052647

    PubMed  CAS  Google Scholar 

  • Shen WF, Hu YL, Uttarwar L, Passegue E, Largman C (2008) MicroRNA-126 regulates HOXA9 by binding to the homeobox. Mol Cell Biol 28(14):4609–4619. doi:10.1128/mcb.01652-07

    PubMed  CAS  Google Scholar 

  • Smirnova L, Gräfe A, Seiler A, Schumacher S, Nitsch R, Wulczyn FG (2005) Regulation of miRNA expression during neural cell specification. Eur J Neurosci 21(6):1469–1477. doi:10.1111/j.1460-9568.2005.03978.x

    PubMed  Google Scholar 

  • Stadtfeld M, Apostolou E, Akutsu H, Fukuda A, Follett P, Natesan S, Kono T, Shioda T, Hochedlinger K (2010) Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells. Nature 465(7295):175–181. doi:10.1038/nature09017

    PubMed  CAS  Google Scholar 

  • Strauss WM, Chen C, Lee C-T, Ridzon D (2006) Nonrestrictive developmental regulation of microRNA gene expression. Mamm Genome 17(8):833–840. doi:10.1007/s00335-006-0025-7

    PubMed  CAS  Google Scholar 

  • Sugatani T, Hruska KA (2007) MicroRNA-223 is a key factor in osteoclast differentiation. J Cell Biochem 101(4):996–999. doi:10.1002/jcb.21335

    PubMed  CAS  Google Scholar 

  • Suh M-R, Lee Y, Kim JY, Kim S-K, Moon S-H, Lee JY, Cha K-Y, Chung HM, Yoon HS, Moon SY (2004) Human embryonic stem cells express a unique set of microRNAs. Dev Biol 270(2):488–498. doi:10.1016/j.ydbio.2004.02.019

    PubMed  CAS  Google Scholar 

  • Sun Q, Zhang Y, Yang G, Chen X, Cao G, Wang J, Sun Y, Zhang P, Fan M, Shao N, Yang X (2008) Transforming growth factor-β-regulated miR-24 promotes skeletal muscle differentiation. Nucleic Acids Res 36(8):2690–2699. doi:10.1093/nar/gkn032

    PubMed  CAS  Google Scholar 

  • Suomi S, Taipaleenmaki H, Seppanen A, Ripatti T, Vaananen K, Hentunen T, Saamanen AM, Laitala-Leinonen T (2008) MicroRNAs regulate osteogenesis and chondrogenesis of mouse bone marrow stromal cells. Gene Regul Syst Biol 2:177–191

    CAS  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676. doi:10.1016/j.cell.2006.07.024

    PubMed  CAS  Google Scholar 

  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872. doi:10.1016/j.cell.2007.11.019

    PubMed  CAS  Google Scholar 

  • Tenedini E, Roncaglia E, Ferrari F, Orlandi C, Bianchi E, Bicciato S, Tagliafico E, Ferrari S (2010) Integrated analysis of microRNA and mRNA expression profiles in physiological myelopoiesis: role of hsa-mir-299-5p in CD34+ progenitor cells commitment. Cell Death Dis 1(2):e28. doi:10.1038/cddis.2010.5

    PubMed  CAS  Google Scholar 

  • Thomson JA (1998) Embryonic stem cell lines derived from human blastocysts. Science 282(5391):1145–1147. doi:10.1126/science.282.5391.1145

    PubMed  CAS  Google Scholar 

  • Turner M, Vigorito E (2008) Regulation of B- and T-cell differentiation by a single microRNA. Biochem Soc Trans 36(3):531. doi:10.1042/bst0360531

    PubMed  CAS  Google Scholar 

  • Tzur G, Levy A, Meiri E, Barad O, Spector Y, Bentwich Z, Mizrahi L, Katzenellenbogen M, Ben-Shushan E, Reubinoff BE, Galun E (2008) MicroRNA expression patterns and function in endodermal differentiation of human embryonic stem cells. PLoS One 3(11):e3726. doi:10.1371/journal.pone.0003726

    PubMed  Google Scholar 

  • van Rooij E, Sutherland LB, Liu N, Williams AH, McAnally J, Gerard RD, Richardson JA, Olson EN (2006) A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Natl Acad Sci 103(48):18255–18260. doi:10.1073/pnas.0608791103

    PubMed  Google Scholar 

  • Velu CS, Baktula AM, Grimes HL (2009) Gfi1 regulates miR-21 and miR-196b to control myelopoiesis. Blood 113(19):4720–4728. doi:10.1182/blood-2008-11-190215

    PubMed  CAS  Google Scholar 

  • Wahid F, Shehzad A, Khan T, Kim YY (2010) MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochim Biophys Acta 1803(11):1231–1243. doi:10.1016/j.bbamcr.2010.06.013

    PubMed  CAS  Google Scholar 

  • Walden TB, Timmons JA, Keller P, Nedergaard J, Cannon B (2009) Distinct expression of muscle-specific MicroRNAs (myomirs) in brown adipocytes. J Cell Physiol 218(2):444–449. doi:10.1002/jcp. 21621

    PubMed  CAS  Google Scholar 

  • Wang Y, Blelloch R (2011) Cell cycle regulation by microRNAs in stem cells. Results Probl Cell Differ 53:459–472. doi:10.1007/978-3-642-19065-0_19

    PubMed  CAS  Google Scholar 

  • Wang Y, Medvid R, Melton C, Jaenisch R, Blelloch R (2007) DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nat Genet 39(3):380–385. doi:10.1038/ng1969

    PubMed  CAS  Google Scholar 

  • Wang Y, Baskerville S, Shenoy A, Babiarz JE, Baehner L, Blelloch R (2008) Embryonic stem cell–specific microRNAs regulate the G1-S transition and promote rapid proliferation. Nat Genet 40(12):1478–1483. doi:10.1038/ng.250

    PubMed  CAS  Google Scholar 

  • Weston MD, Pierce ML, Jensen-Smith HC, Fritzsch B, Rocha-Sanchez S, Beisel KW, Soukup GA (2011) MicroRNA-183 family expression in hair cell development and requirement of microRNAs for hair cell maintenance and survival. Dev Dyn 240(4):808–819. doi:10.1002/dvdy.22591

    PubMed  CAS  Google Scholar 

  • Wienholds E, Koudijs MJ, van Eeden FJM, Cuppen E, Plasterk RHA (2003) The microRNA-producing enzyme Dicer1 is essential for zebrafish development. Nat Genet 35(3):217–218. doi:10.1038/ng1251

    PubMed  CAS  Google Scholar 

  • Wilson KD, Venkatasubrahmanyam S, Jia F, Sun N, Butte AJ, Wu JC (2009) MicroRNA profiling of human-induced pluripotent stem cells. Stem Cells Dev 18(5):749–757. doi:10.1089/scd.2008.0247

    PubMed  CAS  Google Scholar 

  • Wilson KD, Hu S, Venkatasubrahmanyam S, Fu JD, Sun N, Abilez OJ, Baugh JJA, Jia F, Ghosh Z, Li RA, Butte AJ, Wu JC (2010) Dynamic microRNA expression programs during cardiac differentiation of human embryonic stem cells: role for miR-499. Circ Cardiovasc Genet 3(5):426–435. doi:10.1161/circgenetics.109.934281

    PubMed  CAS  Google Scholar 

  • Wong CF, Tellam RL (2008) MicroRNA-26a targets the histone methyltransferase enhancer of Zeste homolog 2 during myogenesis. J Biol Chem 283(15):9836–9843. doi:10.1074/jbc.M709614200

    PubMed  CAS  Google Scholar 

  • Wu L, Belasco JG (2005) Micro-RNA regulation of the mammalian lin-28 gene during neuronal differentiation of embryonal carcinoma cells. Mol Cell Biol 25(21):9198–9208. doi:10.1128/mcb.25.21.9198-9208.2005

    PubMed  CAS  Google Scholar 

  • Xiao C, Calado DP, Galler G, Thai T-H, Patterson HC, Wang J, Rajewsky N, Bender TP, Rajewsky K (2007) MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb. Cell 131(1):146–159. doi:10.1016/j.cell.2007.07.021

    PubMed  CAS  Google Scholar 

  • Xu C, Lu Y, Pan Z, Chu W, Luo X, Lin H, Xiao J, Shan H, Wang Z, Yang B (2007) The muscle-specific microRNAs miR-1 and miR-133 produce opposing effects on apoptosis by targeting HSP60, HSP70 and caspase-9 in cardiomyocytes. J Cell Sci 120(17):3045–3052. doi:10.1242/jcs.010728

    PubMed  CAS  Google Scholar 

  • Yang Z, Wu J (2007) MicroRNAs and regenerative medicine. DNA Cell Biol 26(4):257–264. doi:10.1089/dna.2006.0548

    PubMed  CAS  Google Scholar 

  • Yekta S (2004) MicroRNA-directed cleavage of HOXB8 mRNA. Science 304(5670):594–596. doi:10.1126/science.1097434

    PubMed  CAS  Google Scholar 

  • Yi R, O’Carroll D, Pasolli HA, Zhang Z, Dietrich FS, Tarakhovsky A, Fuchs E (2006) Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs. Nat Genet 38(3):356–362. doi:10.1038/ng1744

    PubMed  CAS  Google Scholar 

  • Yi R, Poy MN, Stoffel M, Fuchs E (2008) A skin microRNA promotes differentiation by repressing ‘stemness’. Nature 452(7184):225–229. doi:10.1038/nature06642

    PubMed  CAS  Google Scholar 

  • Yoo AS, Sun AX, Li L, Shcheglovitov A, Portmann T, Li Y, Lee-Messer C, Dolmetsch RE, Tsien RW, Crabtree GR (2011) MicroRNA-mediated conversion of human fibroblasts to neurons. Nature 476(7359):228–231. doi:10.1038/nature10323

    PubMed  CAS  Google Scholar 

  • Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858):1917–1920. doi:10.1126/science.1151526

    PubMed  CAS  Google Scholar 

  • Yuasa K, Hagiwara Y, Ando M, Nakamura A, Takeda S, Hijikata T (2008) MicroRNA-206 is highly expressed in newly formed muscle fibers implications regarding potential for muscle regeneration and maturation in muscular dystrophy. Cell Struct Funct 33(2):163–169. doi:10.1038/nmeth.1323

    PubMed  CAS  Google Scholar 

  • Zaragosi L-E, Wdziekonski G, Le Brigand K, Waldmann R, Dani C, Barbry P (2011) Small RNA sequencing reveals miR-642a-3p as a novel adipocyte-specific microRNA and miR-30 as a key regulator of human adipogenesis. Genome Biol 12(7):R64. doi:10.1186/gb-2011-12-7-r64

    PubMed  CAS  Google Scholar 

  • Zeng Y, Wagner E, Cullen B (2002) Both natural and designed micro RNAs can inhibit the expression of cognate mRNAs when expressed in human cells. Mol Cell 9(6):1327–1333. doi:10.1016/S1097-2765(02), 00541-5

    PubMed  CAS  Google Scholar 

  • Zhan M, Miller CP, Papayannopoulou T, Stamatoyannopoulos G, Song C-Z (2007) MicroRNA expression dynamics during murine and human erythroid differentiation. Exp Hematol 35(7):1015–1025. doi:10.1016/j.exphem.2007.03.014

    PubMed  CAS  Google Scholar 

  • Zhao Y, Samal E, Srivastava D (2005) Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 436(7048):214–220. doi:10.1038/nature03817

    PubMed  CAS  Google Scholar 

  • Zhou H (2005) An RNA polymerase II construct synthesizes short-hairpin RNA with a quantitative indicator and mediates highly efficient RNAi. Nucleic Acids Res 33(6):e62. doi:10.1093/nar/gni061

    PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank the members of the Lemischka and Moore labs for helpful discussions and feedback. Images of C2C12 myoblast differentiation were kindly provided by Shao-En Ong.

Author information

Authors and Affiliations

  1. Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, The Black Family Stem Cell Institute, New York, NY, USA

    Betty Chang, Ihor R. Lemischka & Christoph Schaniel

  2. Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY, USA

    Ihor R. Lemischka

Authors
  1. Betty Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ihor R. Lemischka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christoph Schaniel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christoph Schaniel .

Editor information

Editors and Affiliations

  1. , New York State Department of Health, Wadsworth Center, New Scotland Avenue 120, New York, 12208, New York, USA

    Bibekanand Mallick

  2. A.J.C. Bose Centenary Building, P-1/12, CIT Scheme - VII M, Bose Institute, Kolkata, 700054, India

    Zhumur Ghosh

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Chang, B., Lemischka, I.R., Schaniel, C. (2012). MicroRNAs in Development, Stem Cell Differentiation, and Regenerative Medicine. In: Mallick, B., Ghosh, Z. (eds) Regulatory RNAs. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-22517-8_17

Download citation

Publish with us

Policies and ethics

Search

Navigation