한국발생생물학회지:발생과생식 (Development and Reproduction)

  • 제14권2호
  • /
  • Pages.43-50
  • /
  • 2010
  • /
  • 2465-9525(pISSN)
  • /
  • 2465-9541(eISSN)
한국발생생물학회 (The Korean Society of Developmental Biology)
권호 표지

줄기세포와 생식세포에서 리프로그래밍 인자에 대한 최근 연구 동향과 전망

Current Progress and Prospects of Reprogramming Factors - Stem Cells vs Germ Cells -

  • 서유미 (차의과학대학교 의생명과학과) ;
  • 이경아 (차의과학대학교 의생명과학과)
  • Seo, You-Mi (Dept. of Biomedical Science, College of Life Science, CHA University) ;
  • Lee, Kyung-Ah (Dept. of Biomedical Science, College of Life Science, CHA University)
  • 투고 : 2010.02.17
  • 심사 : 2010.04.15
  • 발행 : 2010.06.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

최근에 체세포 리프로그래밍 기법을 사용하여 체세포에 몇 가지 전사인자(리프로그래밍 인자)를 넣어줌으로써 유도만능줄기세포(induced pluripotent stem cell, iPS)를 만드는데 성공하였다. 유도만능줄기세포는 배아줄기세포와 유사하게 자가재생 할 수 있는 능력이 있으며, 신체의 모든 타입의 세포로 분화할 수 있는 특징을 가지고 있다. 배아줄기세포와는 달리 면역거부반응이 없다는 점과 윤리적인 문제로부터 자유롭다는 장점이 있어 2006년 Yamanaka 팀이 유도만능줄기세포에 관해 처음 보고한 이후로 이 분야 연구의 급속한 발전이 이루어지고 있다. 하지만 안전성의 문제점 때문에 세포치료제로 사용되기 위해서는 리프로그래밍 인자의 도입 방법 및 새로운 리프로그래밍 인자의 발굴 등 몇 가지 해결해야 할 점들이 남아 있다. 본 종설에서는 유도만능줄기세포를 만드는데 사용된 몇 가지 리프로그래밍 인자에 대해 보고된 연구 내용을 리프로그래밍 인자가 존재하는 세포인 배아줄기세포 및 난자와 배아에서 정리하고자 하며, 리프로그래밍 인자의 연구에 관한 방향에 대해 논의하고자 한다.

Recently induced pluripotent stem (iPS) cells are derived from somatic cells by ectopic expression of several transcription factors (reprogramming factors) using technology of somatic cell reprogramming. iPS cells are able to selfrenew and differentiate into all type of cells in the body similarly to embryonic stem cells. Because iPS cells have advantages that can avoid immune rejection after transplantation and ethical issues unlike embryonic stem cells, research on iPS has made significant progress since the first report by Yamanaka in 2006. Nevertheless of many advantages of iPS, safer methods to introduce reprogramming factors into somatic cells must be developed due to safety concerns regarding viral vectors, and safer reprogramming factors to substitute the oncogenes should be evaluated for clinical application of iPS. Here we discuss the recent progress in reprogramming factors in embryonic stem cells, oocytes, and embryos, and discuss further research for finding new, more reliable and safer reprogramming factors.

키워드

참고문헌

  1. Adhikary S, Eilers M (2005) Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol 6:635-645. https://doi.org/10.1038/nrm1703
  2. Avilion AA, Nicolis SK, Pevny LH, Perez L, Vivian N, Lovell-Badge R (2003) Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev 17:126-140. https://doi.org/10.1101/gad.224503
  3. 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 122:947-956. https://doi.org/10.1016/j.cell.2005.08.020
  4. Cartwright P, McLean C, Sheppard A, Rivett D, Jones K, Dalton S (2005) LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism. Development 132:885-896. https://doi.org/10.1242/dev.01670
  5. Cawley S, Bekiranov S, Ng H, Kapranov P, Sekinger E, Kampa D, Piccolboni A, Sementchenko V, Cheng J, Williams A (2004) Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell 116:499-509. https://doi.org/10.1016/S0092-8674(04)00127-8
  6. Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A (2003) Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113:643-655. https://doi.org/10.1016/S0092-8674(03)00392-1
  7. Chen X, Whitney EM, Gao SY, Yang VW (2003) Transcriptional profiling of Kruppel-like factor 4 reveals a function in cell cycle regulation and epithelial differentiation. J Mol Biol 326:665-677. https://doi.org/10.1016/S0022-2836(02)01449-3
  8. Cowan C, Atienza J, Melton D, Eggan K (2005) Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science 309:1369-1373. https://doi.org/10.1126/science.1116447
  9. Darr H, Mayshar Y, Benvenisty N (2006) Overexpression of NANOG in human ES cells enables feeder-free growth while inducing primitive ectoderm features. Development 133:1193-1201. https://doi.org/10.1242/dev.02286
  10. Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154-156. https://doi.org/10.1038/292154a0
  11. Fernandez P, Frank S, Wang L, Schroeder M, Liu S, Greene J, Cocito A, Amati B (2003) Genomic targets of the human c-Myc protein. Genes Dev 17:1115-1129. https://doi.org/10.1101/gad.1067003
  12. Hanna J, Wernig M, Markoulaki S, Sun CW, Meissner A, Cassady JP, Beard C, Brambrink T, Wu LC, Townes TM, Jaenisch R (2007) Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 318:1920-1923. https://doi.org/10.1126/science.1152092
  13. Hinnebusch BF, Siddique A, Henderson JW, Malo MS, Zhang W, Athaide CP, Abedrapo MA, Chen X, Yang VW, Hodin RA (2004) Enterocyte differentiation marker intestinal alkaline phosphatase is a target gene of the gut-enriched Kruppel-like factor. Am J Physiol Gastrointest Liver Physiol 286:G23-30. https://doi.org/10.1152/ajpgi.00203.2003
  14. Hough SR, Clements I, Welch PJ, Wiederholt KA (2006) Differentiation of mouse embryonic stem cells after RNA interference-mediated silencing of OCT4 and Nanog. Stem Cells 24:1467-1475. https://doi.org/10.1634/stemcells.2005-0475
  15. Hyslop L, Stojkovic M, Armstrong L, Walter T, Stojkovic P, Przyborski S, Herbert M, Murdoch A, Strachan T, Lako M (2005) Downregulation of NANOG induces differentiation of human embryonic stem cells to extraembryonic lineages. Stem Cells 23:1035-1043. https://doi.org/10.1634/stemcells.2005-0080
  16. Ivanova N, Dobrin R, Lu R, Kotenko I, Levorse J, DeCoste C, Schafer X, Lun Y, Lemischka IR (2006) Dissecting self-renewal in stem cells with RNA interference. Nature 442:533-538. https://doi.org/10.1038/nature04915
  17. Jaenisch R, Young R (2008) Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell 132:567-582. https://doi.org/10.1016/j.cell.2008.01.015
  18. Kehler J, Tolkunova E, Koschorz B, Pesce M, Gentile L, Boiani M, Lomeli H, Nagy A, McLaughlin KJ, Scholer HR, Tomilin A (2004) Oct4 is required for primordial germ cell survival. EMBO Rep 5:1078-1083. https://doi.org/10.1038/sj.embor.7400279
  19. Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, Ko S, Yang E, Cha KY, Lanza R, Kim KS (2009) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4:472-476. https://doi.org/10.1016/j.stem.2009.05.005
  20. Knoepfler PS, Zhang XY, Cheng PF, Gafken PR, McMahon SB, Eisenman RN (2006) Myc influences global chromatin structure. EMBO J 25:2723-2734. https://doi.org/10.1038/sj.emboj.7601152
  21. Koopman P, Schepers G, Brenner S, Venkatesh B (2004) Origin and diversity of the SOX transcription factor gene family: genome-wide analysis in Fugu rubripes. Gene 328:177-186. https://doi.org/10.1016/j.gene.2003.12.008
  22. Koscianska E, Baev V, Skreka K, Oikonomaki K, Rusinov V, Tabler M, Kalantidis K (2007) Prediction and preliminary validation of oncogene regulation by miRNAs. BMC Mol Biol 8:79-92. https://doi.org/10.1186/1471-2199-8-79
  23. Lengner CJ, Camargo FD, Hochedlinger K, Welstead GG, Zaidi S, Gokhale S, Scholer HR, Tomilin A, Jaenisch R (2007) Oct4 expression is not required for mouse somatic stem cell self-renewal. Cell Stem Cell 1:403-415. https://doi.org/10.1016/j.stem.2007.07.020
  24. Li J, Pan G, Cui K, Liu Y, Xu S, Pei D (2007) A dominant-negative form of mouse SOX2 induces trophectoderm differentiation and progressive polyploidy in mouse embryonic stem cells. J Biol Chem 282:19481-19492. https://doi.org/10.1074/jbc.M702056200
  25. Li Y, McClintick J, Zhong L, Edenberg HJ, Yoder MC, Chan RJ (2005) Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4. Blood 105:635-637. https://doi.org/10.1182/blood-2004-07-2681
  26. Li Z, Van Calcar S, Qu C, Cavenee W, Zhang M, Ren B (2003) A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells. Proc Natl Acad Sci USA 100:8164-8169. https://doi.org/10.1073/pnas.1332764100
  27. 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 38:431-440. https://doi.org/10.1038/ng1760
  28. Lowry WE, Richter L, Yachechko R, Pyle AD, Tchieu J, Sridharan R, Clark AT, Plath K (2008) Generation of human induced pluripotent stem cells from dermal fibroblasts. Proc Natl Acad Sci USA 105:2883-2888. https://doi.org/10.1073/pnas.0711983105
  29. Maherali N, Sridharan R, Xie W, Utikal J, Eminli S, Arnold K, Stadtfeld M, Yachechko R, Tchieu J, Jaenisch R, Plath K, Hochedlinger K (2007) Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 1:55-70. https://doi.org/10.1016/j.stem.2007.05.014
  30. Masui S, Nakatake Y, Toyooka Y, Shimosato D, Yagi R, Takahashi K, Okochi H, Okuda A, Matoba R, Sharov AA, Ko MS, Niwa H (2007) Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat Cell Biol 9:625-635. https://doi.org/10.1038/ncb1589
  31. Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S (2003) The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113:631-642. https://doi.org/10.1016/S0092-8674(03)00393-3
  32. Moss EG, Lee RC, Ambros V (1997) The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell 88: 637-646. https://doi.org/10.1016/S0092-8674(00)81906-6
  33. Nagy A, Gocza E, Diaz EM, Prideaux VR, Ivanyi E, Markkula M, Rossant J (1990) Embryonic stem cells alone are able to support fetal development in the mouse. Development 110:815-821.
  34. 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 95:379-391. https://doi.org/10.1016/S0092-8674(00)81769-9
  35. Niwa H, Miyazaki J, Smith AG (2000) Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet 24:372-376. https://doi.org/10.1038/74199
  36. O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT (2005) c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435:839-843. https://doi.org/10.1038/nature03677
  37. Paria BC, Dey SK, Andrews GK (1992) Antisense c-myc effects on preimplantation mouse embryo development. Proc Natl Acad Sci USA 89:10051-10055. https://doi.org/10.1073/pnas.89.21.10051
  38. Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, Daley GQ (2008) Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451:141-146. https://doi.org/10.1038/nature06534
  39. Pesce M, Wang X, Wolgemuth DJ, Scholer H (1998) Differential expression of the Oct-4 transcription factor during mouse germ cell differentiation. Mech Dev 71: 89-98. https://doi.org/10.1016/S0925-4773(98)00002-1
  40. Qiu C, Ma Y, Wang J, Peng S, Huang Y (2009) Lin28-mediated post-transcriptional regulation of Oct4 expression in human embryonic stem cells. Nucleic Acids Res 38:1240-1248.
  41. Richards M, Tan SP, Tan JH, Chan WK, Bongso A (2004) The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells 22:51-64. https://doi.org/10.1634/stemcells.22-1-51
  42. Rosner MH, Vigano MA, Ozato K, Timmons PM, Poirier F, Rigby PW, Staudt LM (1990) A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo. Nature 345:686-692. https://doi.org/10.1038/345686a0
  43. Scholer HR, Ruppert S, Suzuki N, Chowdhury K, Gruss P (1990) New type of POU domain in germ line-specific protein Oct-4. Nature 344:435-439. https://doi.org/10.1038/344435a0
  44. Segre JA, Bauer C, Fuchs E (1999) Klf4 is a transcription factor required for establishing the barrier function of the skin. Nat Genet 22:356-360. https://doi.org/10.1038/11926
  45. Shimozaki K, Nakashima K, Niwa H, Taga T (2003) Involvement of Oct3/4 in the enhancement of neuronal differentiation of ES cells in neurogenesis-inducing cultures. Development 130:2505-2512. https://doi.org/10.1242/dev.00476
  46. Suzuki T, Abe K, Inoue A, Aoki F (2009) Expression of c-MYC in nuclear speckles during mouse oocyte growth and preimplantation development. J Reprod Dev 55:491-495. https://doi.org/10.1262/jrd.09-069A
  47. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663-676. https://doi.org/10.1016/j.cell.2006.07.024
  48. Taranger CK, Noer A, Sorensen AL, Hakelien AM, Boquest AC, Collas P (2005) Induction of dedifferentiation, genomewide transcriptional programming, and epigenetic reprogramming by extracts of carcinoma and embryonic stem cells. Mol Biol Cell 16:5719-5735. https://doi.org/10.1091/mbc.E05-06-0572
  49. Viswanathan SR, Daley GQ, Gregory RI (2008) Selective blockade of microRNA processing by Lin28. Science 320:97-100. https://doi.org/10.1126/science.1154040
  50. Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385:810-813. https://doi.org/10.1038/385810a0
  51. Yang DH, Moss EG (2003) Temporally regulated expression of Lin-28 in diverse tissues of the developing mouse. Gene Expr Patterns 3:719-726. https://doi.org/10.1016/S1567-133X(03)00140-6
  52. Yeom YI, Fuhrmann G, Ovitt CE, Brehm A, Ohbo K, Gross M, Hubner K, Scholer HR (1996) Germline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells. Development 122: 881-894.
  53. Zaehres H, Lensch MW, Daheron L, Stewart SA, Itskovitz-Eldor J, Daley GQ (2005) High-efficiency RNA interference in human embryonic stem cells. Stem Cells 23:299-305. https://doi.org/10.1634/stemcells.2004-0252
  54. Zhang W, Geiman DE, Shields JM, Dang DT, Mahatan CS, Kaestner KH, Biggs JR, Kraft AS, Yang VW (2000) The gut-enriched Kruppel-like factor (Kruppellike factor 4) mediates the transactivating effect of p53 on the p21WAF1/Cip1 promoter. J Biol Chem 275: 18391-18398. https://doi.org/10.1074/jbc.C000062200