A network of heterochronic genes including Imp1 regulates temporal changes in stem cell properties

eLife

Volumn 2013, Issue 2, 2013, Pages

  Nishino, Jinsuke ^a,b   Kim, Sunjung ^c,d   Zhu, Yuan ^c,d   Zhu, Hao ^a,b   Morrison, Sean J ^a,b  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^c UNIVERSITY OF MICHIGAN   (United States)

^d UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIN D1; CYCLIN D2; EOMESODERMIN; HIGH MOBILITY GROUP A2 PROTEIN; IMP1 PROTEIN; IMP1 PROTEIN, MOUSE; MICRORNA; MIRNLET7 MICRORNA, MOUSE; OLIGODENDROCYTE MYELIN GLYCOPROTEIN; RNA BINDING PROTEIN; SYNAPTOTAGMIN I; TRANSCRIPTION FACTOR PAX6; UNCLASSIFIED DRUG; WNT PROTEIN;

ANIMAL; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAIN SIZE; CELL PROLIFERATION; CELL RENEWAL; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; CYTOLOGY; DNA LIBRARY; EMBRYO; FEMALE; GENE EXPRESSION REGULATION; GENETICS; IMMUNOCYTOCHEMISTRY; IMMUNOHISTOCHEMISTRY; IN SITU HYBRIDIZATION; METABOLISM; MOUSE; MOUSE MUTANT; NEURAL STEM CELL; NONHUMAN; PHYSIOLOGY; POLYSOME; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; RNA PROCESSING; SOUTHERN BLOTTING; TELENCEPHALON; TRANSGENIC MOUSE; VIRUS INFECTION; WESTERN BLOTTING;

ANIMALS; CYTOLOGY; GENE EXPRESSION REGULATION; GENETICS; HMGA2 PROTEIN; METABOLISM; MICE; MICE, TRANSGENIC; MICRORNAS; NEURAL STEM CELLS; PHYSIOLOGY; REAL-TIME POLYMERASE CHAIN REACTION; RNA PROCESSING, POST-TRANSCRIPTIONAL; RNA-BINDING PROTEINS; TELENCEPHALON;

EID: 84887368980     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.00924.001     Document Type: Article

References (88)

1. Alvarez-Buylla A, Lim DA. 2004. For the long run: maintaining germinal niches in the adult brain. Neuron 41:683-6. doi: 10.1016/S0896-6273(04)00111-4.
2. Atlas R, Behar L, Elliott E, Ginzburg I. 2004. The insulin-like growth factor mRNA binding-protein IMP-1 and the Ras-regulatory protein G3BP associate with tau mRNA and HuD protein in differentiated P19 neuronal cells. J Neurochem 89:613-26. doi: 10.1111/j.1471-4159.2004.02371.x.
3. Atlas R, Behar L, Sapoznik S, Ginzburg I. 2007. Dynamic association with polysomes during P19 neuronal differentiation and an untranslated-region-dependent translation regulation of the tau mRNA by the tau mRNA-associated proteins IMP1, HuD, and G3BP1. J Neurosci Res 85:173-83. doi: 10.1002/jnr.21099.
4. Bonaguidi MA, Wheeler MA, Shapiro JS, Stadel RP, Sun GJ, Ming GL, et al. 2011. In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics. Cell 145:1142-55. doi: 10.1016/j.cell.2011.05.024.
5. Boyerinas B, Park SM, Shomron N, Hedegaard MM, Vinther J, Andersen JS, et al. 2008. Identification of let-7-regulated oncofetal genes. Cancer Res 68:2587-91. doi: 10.1158/0008-5472.CAN-08-0264.
6. Brault V, Moore R, Kutsch S, Ishibashi M, Rowitch DH, McMahon AP, et al. 2001. Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development. Development 128:1253-64.
7. Cavazzana-Calvo M, Payen E, Negre O, Wang G, Hehir K, Fusil F, et al. 2010. Transfusion independence and HMGA2 activation after gene therapy of human beta-thalassaemia. Nature 467:318-22. doi: 10.1038/nature09328.
8. Chenn A, Walsh CA. 2002. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science 297:365-9. doi: 10.1126/science.1074192.
9. Cho J, Chang H, Kwon SC, Kim B, Kim Y, Choe J, et al. 2012. LIN28A is a suppressor of ER-associated translation in embryonic stem cells. Cell 151:765-77. doi: 10.1016/j.cell.2012.10.019.
10. Copeland NG, Jenkins NA, Court DL. 2001. Recombineering: a powerful new tool for mouse functional genomics. Nat Rev Genet 2:769-79. doi: 10.1038/35093556.
11. Dehay C, Kennedy H. 2007. Cell-cycle control and cortical development. Nat Rev Neurosci 8:438-50. doi: 10.1038/nrn2097.
12. Dickinson ME, Krumlauf R, McMahon AP. 1994. Evidence for a mitogenic effect of Wnt-1 in the developing mammalian central nervous system. Development 120:1453-71.
13. Doyle GA, Betz NA, Leeds PF, Fleisig AJ, Prokipcak RD, Ross J. 1998. The c-myc coding region determinant-binding protein: a member of a family of KH domain RNA-binding proteins. Nucleic Acids Res 26:5036-44. doi: 10.1093/nar/26.22.5036.
14. Encinas JM, Michurina TV, Peunova N, Park JH, Tordo J, Peterson DA, et al. 2011. Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus. Cell Stem Cell 8:566-79. doi: 10.1016/j.stem.2011.03.010.
15. Enwere E, Shingo T, Gregg C, Fujikawa H, Ohta S, Weiss S. 2004. Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. J Neurosci 24:8354-65. doi: 10.1523/JNEUROSCI.2751-04.2004.
16. Farina KL, Huttelmaier S, Musunuru K, Darnell R, Singer RH. 2003. Two ZBP1 KH domains facilitate beta-actin mRNA localization, granule formation, and cytoskeletal attachment. J Cell Biol 160:77-87. doi: 10.1083/jcb.200206003.
17. Gu W, Wells AL, Pan F, Singer RH. 2008. Feedback regulation between zipcode binding protein 1 and beta-catenin mRNAs in breast cancer cells. Mol Cell Biol 28:4963-74. doi: 10.1128/MCB.00266-08.
18. Gulacsi AA, Anderson SA. 2008. Beta-catenin-mediated Wnt signaling regulates neurogenesis in the ventral telencephalon. Nat Neurosci 11:1383-91. doi: 10.1038/nn.2226.
19. Hafner M, Landthaler M, Burger L, Khorshid M, Hausser J, Berninger P, et al. 2010. Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141:129-41. doi: 10.1016/j.cell.2010.03.009.
20. Hammer NA, Hansen TO, Byskov AG, Rajpert-De Meyts E, Grondahl ML, Bredkjaer HE, et al. 2005. Expression of IGF-II mRNA-binding proteins (IMPs) in gonads and testicular cancer. Reproduction 130:203-12. doi: 10.1530/rep.1.00664.
21. Hansen TV, Hammer NA, Nielsen J, Madsen M, Dalbaeck C, Wewer UM, et al. 2004. Dwarfism and impaired gut development in insulin-like growth factor II mRNA-binding protein 1-deficient mice. Mol Cell Biol 24:4448-64. doi: 10.1128/MCB.24.10.4448-4464.2004.
22. He S, Nakada D, Morrison SJ. 2009. Mechanisms of stem cell self-renewal. Ann Rev Cell Dev Biol 25:377-406. doi: 10.1146/annurev.cellbio.042308.113248.
23. Hebert JM, Hayhurst M, Marks ME, Kulessa H, Hogan BL, Mcconnell SK. 2003. BMP ligands act redundantly to pattern the dorsal telencephalic midline. Genesis 35:214-9. doi: 10.1002/gene.10183.
24. Heo I, Joo C, Cho J, Ha M, Han J, Kim VN. 2008. Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA. Mol Cell 32:276-84. doi: 10.1016/j.molcel.2008.09.014.
25. Ikeda K, Mason PJ, Bessler M. 2011. 3'UTR-truncated Hmga2 cDNA causes MPN-like hematopoiesis by conferring a clonal growth advantage at the level of HSC in mice. Blood 117:5860-9. doi: 10.1182/blood-2011-02-334425.
26. Ikeya M, Lee SM, Johnson JE, McMahon AP, Takada S. 1997. Wnt signalling required for expansion of neural crest and CNS progenitors. Nature 389:966-70. doi: 10.1038/40146.
27. Ioannidis P, Kottaridi C, Dimitriadis E, Courtis N, Mahaira L, Talieri M, et al. 2004. Expression of the RNA-binding protein CRD-BP in brain and non-small cell lung tumors. Cancer Lett 209:245-50. doi: 10.1016/j.canlet.2003.12.015.
28. Janzen V, Forkert R, Fleming HE, Saito Y, Waring MT, Dombkowski DM, et al. 2006. Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443:421-6. doi: 10.1038/nature05159.
29. Jho EH, Zhang T, Domon C, Joo CK, Freund JN, Costantini F. 2002. Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol Cell Biol 22:1172-83. doi: 10.1128/MCB.22.4.1172-1183.2002.
30. Jønson L, Vikesaa J, Krogh A, Nielsen LK, Hansen T, Borup R, et al. 2007. Molecular composition of IMP1 ribonucleoprotein granules. Mol Cell Proteomics 6:798-811. doi: 10.1074/mcp.M600346-MCP200.
31. Juliano C, Wang J, Lin H. 2011. Uniting germline and stem cells: the function of Piwi proteins and the piRNA pathway in diverse organisms. Ann Rev Genet 45:447-69. doi: 10.1146/annurev-genet-110410-132541.
32. Kharas MG, Lengner CJ, Al-Shahrour F, Bullinger L, Ball B, Zaidi S, et al. 2010. Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia. Nat Med 16:903-8. doi: 10.1038/nm.2187.
33. Kimble J, Crittenden SL. 2007. Controls of germline stem cells, entry into meiosis, and the sperm/oocyte decision in Caenorhabditis elegans. Ann Rev Cell Dev Biol 23:405-33. doi: 10.1146/annurev.cellbio.23.090506.123326.
34. Krishnamurthy J, Ramsey MR, Ligon KL, Torrice C, Koh A, Bonner-Weir S, et al. 2006. p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 443:453-7. doi: 10.1038/nature05092.
35. Kuhn HG, Dickinson-Anson H, Gage FH. 1996. Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16:2027-33.
36. Kuwabara T, Hsieh J, Muotri A, Yeo G, Warashina M, Lie DC, et al. 2009. Wnt-mediated activation of NeuroD1 and retro-elements during adult neurogenesis. Nat Neurosci 12:1097-105. doi: 10.1038/nn.2360.
37. Lange C, Huttner WB, Calegari F. 2009. Cdk4/cyclinD1 overexpression in neural stem cells shortens G1, delays neurogenesis, and promotes the generation and expansion of basal progenitors. Cell Stem Cell 5:320-31. doi: 10.1016/j.stem.2009.05.026.
38. Langmead B, Trapnell C, Pop M, Salzberg SL. 2009. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10:R25. doi: 10.1186/gb-2009-10-3-r25.
39. Li Z, Gilbert JA, Zhang Y, Zhang M, Qiu Q, Ramanujan K, et al. 2012. An HMGA2-IGF2BP2 axis regulates myoblast proliferation and myogenesis. Dev Cell 23:1176-88. doi: 10.1016/j.devcel.2012.10.019.
40. Liu P, Jenkins NA, Copeland NG. 2003. A highly efficient recombineering-based method for generating conditional knockout mutations. Genome Res 13:476-84. doi: 10.1101/gr.749203.
41. Machon O, Backman M, Machonova O, Kozmik Z, Vacik T, Andersen L, et al. 2007. A dynamic gradient of Wnt signaling controls initiation of neurogenesis in the mammalian cortex and cellular specification in the hippocampus. Dev Biol 311:223-37. doi: 10.1016/j.ydbio.2007.08.038.
42. Machon O, Van Den Bout CJ, Backman M, Kemler R, Krauss S. 2003. Role of beta-catenin in the developing cortical and hippocampal neuroepithelium. Neuroscience 122:129-43. doi: 10.1016/S0306-4522(03)00519-0.
43. Malatesta P, Hack MA, Hartfuss E, Kettenmann H, Klinkert W, Kirchhoff F, et al. 2003. Neuronal or glial progeny: regional differences in radial glia fate. Neuron 37:751-64. doi: 10.1016/S0896-6273(03)00116-8.
44. Maslov AY, Barone TA, Plunkett RJ, Pruitt SC. 2004. Neural stem cell detection, characterization, and age-related changes in the subventricular zone of mice. J Neurosci 24:1726-33. doi: 10.1523/JNEUROSCI.4608-03.2004.
45. McMahon AP, Bradley A. 1990. The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain. Cell 62:1073-85. doi: 10.1016/0092-8674(90)90385-R.
46. McMahon AP, Joyner AL, Bradley A, McMahon JA. 1992. The midbrain-hindbrain phenotype of Wnt-1-/Wnt-1-mice results from stepwise deletion of engrailed-expressing cells by 9.5 days postcoitum. Cell 69:581-95. doi: 10.1016/0092-8674(92)90222-X.
47. Megason SG, McMahon AP. 2002. A mitogen gradient of dorsal midline Wnts organizes growth in the CNS. Development 129:2087-98.
48. Melton C, Judson RL, Blelloch R. 2010. Opposing microRNA families regulate self-renewal in mouse embryonic stem cells. Nature 463:621-6. doi: 10.1038/nature08725.
49. Molofsky AV, He S, Bydon M, Morrison SJ, Pardal R. 2005. Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways. Genes Dev 19:1432-7. doi: 10.1101/gad.1299505.
50. Molofsky AV, Slutsky SG, Joseph NM, He S, Pardal R, Krishnamurthy J, et al. 2006. Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443:448-52. doi: 10.1038/nature05091.
51. Mutch CA, Schulte JD, Olson E, Chenn A. 2010. Beta-catenin signaling negatively regulates intermediate progenitor population numbers in the developing cortex. PLOS ONE 5:e12376. doi: 10.1371/journal.pone.0012376.
52. Newman MA, Thomson JM, Hammond SM. 2008. Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing. RNA 14:1539-49. doi: 10.1261/rna.1155108.
53. Nielsen FC, Nielsen J, Kristensen MA, Koch G, Christiansen J. 2002. Cytoplasmic trafficking of IGF-II mRNA-binding protein by conserved KH domains. J Cell Sci 115:2087-97.
54. Nielsen J, Christiansen J, Lykke-Andersen J, Johnsen AH, Wewer UM, Nielsen FC. 1999. A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development. Mol Cell Biol 19:1262-70.
55. Nishino J, Kim I, Chada K, Morrison SJ. 2008. Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf Expression. Cell 135:227-39. doi: 10.1016/j.cell.2008.09.017.
56. Noubissi FK, Elcheva I, Bhatia N, Shakoori A, Ougolkov A, Liu J, et al. 2006. CRD-BP mediates stabilization of betaTrCP1 and c-myc mRNA in response to beta-catenin signalling. Nature 441:898-901. doi: 10.1038/nature04839.
57. Okano H, Kawahara H, Toriya M, Nakao K, Shibata S, Imai T. 2005. Function of RNA-binding protein Musashi-1 in stem cells. Exp Cell Res 306:349-56. doi: 10.1016/j.yexcr.2005.02.021.
58. Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, et al. 2000. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 408:86-9. doi: 10.1038/35040556.
59. Qu Q, Sun G, Li W, Yang S, Ye P, Zhao C, et al. 2010. Orphan nuclear receptor TLX activates Wnt/beta-catenin signalling to stimulate neural stem cell proliferation and self-renewal. Nat Cell Biol 12:31-40. doi: 10.1038/ncb2001.
60. Roberts A, Trapnell C, Donaghey J, Rinn JL, Pachter L. 2009. Improving RNA-Seq expression estimates by correcting for fragment bias. Genome Biol 12:R22. doi: 10.1186/gb-2011-12-3-r22.
61. Rodriguez CI, Buchholz F, Galloway J, Sequerra R, Kasper J, Ayala R, et al. 2000. High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nature Genet 25:139-40. doi: 10.1038/75973.
62. Roush S, Slack FJ. 2008. The let-7 family of microRNAs. Trends Cell Biol 18:505-16. doi: 10.1016/j.tcb.2008.07.007.
63. Rybak A, Fuchs H, Smirnova L, Brandt C, Pohl EE, Nitsch R, et al. 2008. A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment. Nat Cell Biol 10:987-93. doi: 10.1038/ncb1759.
64. Sakakibara S, Nakamura Y, Yoshida T, Shibata S, Koike M, Takano H, et al. 2002. RNA-binding protein Musashi family: roles for CNS stem cells and a subpopulation of ependymal cells revealed by targeted disruption and antisense ablation. Proc Natl Acad Sci USA 99:15194-9. doi: 10.1073/pnas.232087499.
65. Salomoni P, Calegari F. 2010. Cell cycle control of mammalian neural stem cells: putting a speed limit on G1. Trends Cell Biol 20:233-43. doi: 10.1016/j.tcb.2010.01.006.
66. Seib DRM, Corsini NS, Ellwanger K, Plaas C, Mateos A, Pitzer C, et al. 2013. Loss of Dickkopf-1 restores neurogenesis in old age and counteracts cognitive decline. Cell Stem Cell 12:204-14. doi: 10.1016/j.stem.2012.11.010.
67. Shen Y, Wollam J, Magner D, Karalay O, Antebi A. 2012. A steroid receptor-microRNA switch regulates life span in response to signals from the gonad. Science 338:1472-6. doi: 10.1126/science.1228967.
68. Shibata H, Toyama K, Shioya H, Ito M, Hirota M, Hasegawa S, et al. 1997. Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene. Science 278:120-3. doi: 10.1126/science.278.5335.120.
69. Stemple DL, Anderson DJ. 1992. Isolation of a stem cell for neurons and glia from the mammalian neural crest. Cell 71:973-85. doi: 10.1016/0092-8674(92)90393-Q.
70. Tessier CR, Doyle GA, Clark BA, Pitot HC, Ross J. 2004. Mammary tumor induction in transgenic mice expressing an RNA-binding protein. Cancer Res 64:209-14. doi: 10.1158/0008-5472.CAN-03-2927.
71. Toledano H, D'alterio C, Czech B, Levine E, Jones DL. 2012. The let-7-Imp axis regulates ageing of the Drosophila testis stem-cell niche. Nature 485:605-10. doi: 10.1038/nature11061.
72. Trapnell C, Pachter L, Salzberg SL. 2009. TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25:1105-11. doi: 10.1093/bioinformatics/btp120.
73. Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, Van Baren MJ, et al. 2010. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol 28:511-5. doi: 10.1038/nbt.1621.
74. Tronche F, Kellendonk C, Kretz O, Gass P, Anlag K, Orban PC, et al. 1999. Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat Genet 23:99-103. doi: 10.1038/12703.
75. Viswanathan SR, Daley GQ. 2010. Lin28: a microRNA regulator with a macro role. Cell 140:445-9. doi: 10.1016/j.cell.2010.02.007.
76. Viswanathan SR, Daley GQ, Gregory RI. 2008. Selective blockade of microRNA processing by Lin28. Science 320:97-100. doi: 10.1126/science.1154040.
77. West JA, Viswanathan SR, Yabuuchi A, Cunniff K, Takeuchi A, Park IH, et al. 2009. A role for Lin28 in primordial germ-cell development and germ-cell malignancy. Nature 460:909-13. doi: 10.1038/nature08210.
78. Wilbert ML, Huelga SC, Kapeli K, Stark TJ, Liang TY, Chen SX, et al. 2012. LIN28 binds messenger RNAs at GGAGA motifs and regulates splicing factor abundance. Mol Cell 48:195-206. doi: 10.1016/j.molcel.2012.08.004.
79. Woodhead GJ, Mutch CA, Olson EC, Chenn A. 2006. Cell-autonomous beta-catenin signaling regulates cortical precursor proliferation. J Neurosci 26:12620-30. doi: 10.1523/JNEUROSCI.3180-06.2006.
80. Wrobel CN, Mutch CA, Swaminathan S, Taketo MM, Chenn A. 2007. Persistent expression of stabilized beta-catenin delays maturation of radial glial cells into intermediate progenitors. Dev Biol 309:285-97. doi: 10.1016/j.ydbio.2007.07.013.
81. Yisraeli JK. 2005. VICKZ proteins: a multi-talented family of regulatory RNA-binding proteins. Biol Cell 97:87-96. doi: 10.1042/BC20040151.
82. Zechner D, Fujita Y, Hulsken J, Muller T, Walther I, Taketo MM, et al. 2003. beta-Catenin signals regulate cell growth and the balance between progenitor cell expansion and differentiation in the nervous system. Dev Biol 258:406-18. doi: 10.1016/S0012-1606(03)00123-4.
83. Zhao C, Deng W, Gage FH. 2008. Mechanisms and functional implications of adult neurogenesis. Cell 132:645-60. doi: 10.1016/j.cell.2008.01.033.
84. Zhao C, Sun G, Li S, Lang MF, Yang S, Li W, et al. 2010. MicroRNA let-7b regulates neural stem cell proliferation and differentiation by targeting nuclear receptor TLX signaling. Proc Natl Acad Sci USA 107:1876-81. doi: 10.1073/pnas.0908750107.
85. Zhou CJ, Borello U, Rubenstein JL, Pleasure SJ. 2006. Neuronal production and precursor proliferation defects in the neocortex of mice with loss of function in the canonical Wnt signaling pathway. Neuroscience 142:1119-31. doi: 10.1016/j.neuroscience.2006.07.007.
86. Zhou X, Benson KF, Ashar HR, Chada K. 1995. Mutation responsible for the mouse pygmy phenotype in the developmentally regulated factor HMGI-C. Nature 376:771-4. doi: 10.1038/376771a0.
87. Zhu H, Shah S, Shyh-Chang N, Shinoda G, Einhorn WS, Viswanathan SR, et al. 2010. Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies. Nature Genet 42:626-30. doi: 10.1038/ng.593.
88. Zhu H, Shyh-Chang N, Segre AV, Shinoda G, Shah SP, Einhorn WS, et al. 2011. The Lin28/let-7 axis regulates glucose metabolism. Cell 147:81-94. doi: 10.1016/j.cell.2011.08.033.