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Concise Review: Isoforms of OCT4 Contribute to the Confusing Diversity in Stem Cell Biology
Xia Wang, Jianwu Dai
Stem Cells · 2010 · Review
Abstract
The human OCT4 gene can generate at least three transcripts (OCT4A, OCT4B, and OCT4B1) and four protein isoforms (OCT4A, OCT4B-190, OCT4B-265, and OCT4B-164) by alternative splicing and alternative translation initiation. OCT4A is a transcription factor responsible for the pluripotency properties of embryonic stem (ES) cells. While OCT4B cannot sustain ES cell self-renewal, it may respond to cell stresses. Yet, the function of OCT4B1 is still unclear. Lack of distinction of OCT4 isoforms could lead to confusions and controversies on OCT4 in various tissues and cells. One important issue we emphasize in this review article is that alternatively spliced transcripts and alternative translation products of OCT4 exhibit diverse expression patterns and functions. Furthermore, simple approaches and methods to detect and distinguish OCT4 isoforms are discussed. This article underscores the importance of identifying and discriminating the expression and functions of OCT4 isoforms in stem cell research.
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References 85
- 1.
Murry CE, Keller G. Differentiation of embryonic stem cells to clinically relevant populations: Lessons from embryonic development. Cell. 2008;132:661-680.
Not in our library10.1016/j.cell.2008.02.008
- 2.
Weissman IL. Translating stem and progenitor cell biology to the clinic: Barriers and opportunities. Science (New York, NY). 2000;287:1442-1446.
Not in our library10.1126/science.287.5457.1442
- 3.
Yamanaka S. A fresh look at iPS cells. Cell. 2009;137:13-17.
Not in our library10.1016/j.cell.2009.03.034
- 4.
Nichols J, Zevnik B, Anastassiadis K, et al. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell. 1998;95:379-391.
Not in our library10.1016/s0092-8674(00)81769-9
- 5.
Niwa H, Miyazaki J, Smith AG. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet. 2000;24:372-376.
Not in our library10.1038/74199
- 6.
Boyer LA, Lee TI, Cole MF, et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 2005;122:947-956.
Not in our library10.1016/j.cell.2005.08.020
- 7.
Yu J, Vodyanik MA, Smuga-Otto K, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science (New York, NY). 2007;318:1917-1920.
Not in our library10.1126/science.1151526
- 8.
Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861-872.
Not in our library10.1016/j.cell.2007.11.019
- 9.
Park IH, Zhao R, West JA, et al. Reprogramming of human somatic cells to pluripotency with defined factors. Nature. 2008;451:141-146.
Not in our library10.1038/nature06534
- 10.
Takeda J, Seino S, Bell GI. Human Oct3 gene family: cDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues. Nucleic Acids Res. 1992;20:4613-4620.
Not in our library10.1093/nar/20.17.4613
- 11.
Atlasi Y, Mowla SJ, Ziaee SA, et al. OCT4 spliced variants are differentially expressed in human pluripotent and nonpluripotent cells. Stem Cells. 2008;26:3068-3074.
Not in our library10.1634/stemcells.2008-0530
- 12.
Lee J, Kim HK, Rho JY, et al. The human OCT-4 isoforms differ in their ability to confer self-renewal. J Biol Chem. 2006;281:33554-33565.
Not in our library10.1074/jbc.m603937200
- 13.
Abdel-Rahman B, Fiddler M, Rappolee D, et al. Expression of transcription regulating genes in human preimplantation embryos. Hum Reprod (Oxford, England). 1995;10:2787-2792.
Not in our library10.1093/oxfordjournals.humrep.a135792
- 14.
Hansis C, Grifo JA, Krey LC. Oct-4 expression in inner cell mass and trophectoderm of human blastocysts. Mol Hum Reprod. 2000;6:999-1004.
Not in our library10.1093/molehr/6.11.999
- 15.
Richards M, Tan SP, Tan JH, et al. The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells. 2004;22:51-64.
Not in our library10.1634/stemcells.22-1-51
- 16.
Hay DC, Sutherland L, Clark J, et al. Oct-4 knockdown induces similar patterns of endoderm and trophoblast differentiation markers in human and mouse embryonic stem cells. Stem Cells. 2004;22:225-235.
Not in our library10.1634/stemcells.22-2-225
- 17.
Matin MM, Walsh JR, Gokhale PJ, et al. Specific knockdown of Oct4 and beta2-microglobulin expression by RNA interference in human embryonic stem cells and embryonic carcinoma cells. Stem Cells (Dayton, OH). 2004;22:659-668.
Not in our library10.1634/stemcells.22-5-659
- 18.
Cauffman G, Van de Velde H, Liebaers I, et al. Oct-4 mRNA and protein expression during human preimplantation development. Mol Hum Reprod. 2005;11:173-181.
Not in our library10.1093/molehr/gah155
- 19.
Cauffman G, Liebaers I, Van Steirteghem A, et al. POU5F1 isoforms show different expression patterns in human embryonic stem cells and preimplantation embryos. Stem Cells (Dayton, OH). 2006;24:2685-2691.
Not in our library10.1634/stemcells.2005-0611
- 20.
Wang X, Zhao Y, Xiao Z, et al. Alternative translation of OCT4 by an internal ribosome entry site and its novel function in stress response. Stem Cells. 2009;27:1265-1275.
Not in our library10.1002/stem.58
- 21.
Papamichos SI, Kotoula V, Tarlatzis BC, et al. OCT4B1 isoform: the novel OCT4 alternative spliced variant as a putative marker of stemness. Mol Hum Reprod. 2009;15:269-270.
Not in our library10.1093/molehr/gap018
- 22.
Zaehres H, Lensch MW, Daheron L, et al. High-efficiency RNA interference in human embryonic stem cells. Stem Cells (Dayton, OH). 2005;23:299-305.
Not in our library10.1634/stemcells.2004-0252
- 23.
Lengner CJ, Camargo FD, Hochedlinger K, et al. Oct4 expression is not required for mouse somatic stem cell self-renewal. Cell Stem Cell. 2007;1:403-415.
Not in our library10.1016/j.stem.2007.07.020
- 24.
Zangrossi S, Marabese M, Broggini M, et al. Oct-4 expression in adult human differentiated cells challenges its role as a pure stem cell marker. Stem Cells. 2007;25:1675-1680.
Not in our library10.1634/stemcells.2006-0611
- 25.
Tai MH, Chang CC, Kiupel M, et al. Oct4 expression in adult human stem cells: Evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis. 2005;26:495-502.
Not in our library10.1093/carcin/bgh321
- 26.
Liedtke S, Enczmann J, Waclawczyk S, et al. Oct4 and its pseudogenes confuse stem cell research. Cell Stem Cell. 2007;1:364-366.
Not in our library10.1016/j.stem.2007.09.003
- 27.
Liedtke S, Stephan M, Kogler G. Oct4 expression revisited: Potential pitfalls for data misinterpretation in stem cell research. Biol Chem. 2008;389:845-850.
Not in our library10.1515/bc.2008.098
- 28.
de Jong J, Looijenga LH. Stem cell marker OCT3/4 in tumor biology and germ cell tumor diagnostics: History and future. Crit Rev Oncog. 2006;12:171-203.
Not in our library10.1615/critrevoncog.v12.i3-4.10
- 29.
Lengner CJ, Welstead GG, Jaenisch R. The pluripotency regulator Oct4: A role in somatic stem cells? Cell Cycle (Georgetown, TX). 2008;7:725-728.
Not in our library10.4161/cc.7.6.5573
- 30.
Kotoula V, Papamichos SI, Lambropoulos AF. Revisiting OCT4 expression in peripheral blood mononuclear cells. Stem Cells. 2008;26:290-291.
Not in our library10.1634/stemcells.2007-0726
- 31.
Cesselli D, Beltrami AP, Rigo S, et al. Multipotent progenitor cells are present in human peripheral blood. Circ Res. 2009;104:1225-1234.
Not in our library10.1161/circresaha.109.195859
- 32.
Chang CC, Shieh GS, Wu P, et al. Oct-3/4 expression reflects tumor progression and regulates motility of bladder cancer cells. Cancer Res. 2008;68:6281-6291.
Not in our library10.1158/0008-5472.can-08-0094
- 33.
Hu T, Liu S, Breiter DR, et al. Octamer 4 small interfering RNA results in cancer stem cell-like cell apoptosis. Cancer Res. 2008;68:6533-6540.
Not in our library10.1158/0008-5472.can-07-6642
- 34.
Krishnan BR, Jamry I, Chaplin DD. Feature mapping of the HLA class I region: Localization of the POU5F1 and TCF19 genes. Genomics. 1995;30:53-58.
Not in our library10.1006/geno.1995.0008
- 35.
Guillaudeux T, Mattei MG, Depetris D, et al. In situ hybridization localizes the human OTF3 to chromosome 6p21.3→p22 and OTF3L to 12p13. Cytogenet Cell Genet. 1993;63:212-214.
Not in our library10.1159/000133537
- 36.
Herr W, Cleary MA. The POU domaVersatility in transcriptional regulation by a flexible two-in-one DNA-binding domain. Genes Dev. 1995;9:1679-1693.
Not in our library10.1101/gad.9.14.1679
- 37.
Sturm RA, Herr W. The POU domain is a bipartite DNA-binding structure. Nature. 1988;336:601-604.
Not in our library10.1038/336601a0
- 38.
Brehm A, Ohbo K, Scholer H. The carboxy-terminal transactivation domain of Oct-4 acquires cell specificity through the POU domain. Mol Cell Biol. 1997;17:154-162.
Not in our library10.1128/mcb.17.1.154
- 39.
Pain D, Chirn GW, Strassel C, et al. Multiple retropseudogenes from pluripotent cell-specific gene expression indicates a potential signature for novel gene identification. J Biol Chem. 2005;280:6265-6268.
Not in our library10.1074/jbc.c400587200
- 40.
Harrison PM, Zheng D, Zhang Z, et al. Transcribed processed pseudogenes in the human genome: An intermediate form of expressed retrosequence lacking protein-coding ability. Nucleic Acids Res. 2005;33:2374-2383.
Not in our library10.1093/nar/gki531
- 41.
Panagopoulos I, Moller E, Isaksson M, et al. A PCR/restriction digestion assay for the detection of the transcript variants 1 and 2 of POU5F1. Genes Chromosomes Cancer. 2008;47:521-529.
Not in our library10.1002/gcc.20555
- 42.
Suo G, Han J, Wang X, et al. Oct4 pseudogenes are transcribed in cancers. Biochem Biophys Res Commun. 2005;337:1047-1051.
Not in our library10.1016/j.bbrc.2005.09.157
- 43.
Seo KW, Lee SR, Bhandari DR, et al. OCT4A contributes to the stemness and multi-potency of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs). Biochem Biophys Res Commun. 2009;384:120-125.
Not in our library10.1016/j.bbrc.2009.04.094
- 44.
Sotomayor P, Godoy A, Smith GJ, et al. Oct4A is expressed by a subpopulation of prostate neuroendocrine cells. Prostate. 2009;69:401-410.
Not in our library10.1002/pros.20895
- 45.
Kwok S, Kellogg DE, McKinney N, et al. Effects of primer-template mismatches on the polymerase chain reaction: Human immunodeficiency virus type 1 model studies. Nucleic Acids Res. 1990;18:999-1005.
Not in our library10.1093/nar/18.4.999
- 46.
Gale JM, Tafoya GB. Evaluation of 15 polymerases and phosphorothioate primer modification for detection of UV-induced C:G to T:A mutations by allele-specific PCR. Photochem Photobiol. 2004;79:461-469.
Not in our library10.1562/2003-11-12-ra.1
- 47.
Panagopoulos I, Moller E, Collin A, et al. The POU5F1P1 pseudogene encodes a putative protein similar to POU5F1 isoform 1. Oncol Rep. 2008;20:1029-1033.
Not in our library
- 48.
Bugler B, Amalric F, Prats H. Alternative initiation of translation determines cytoplasmic or nuclear localization of basic fibroblast growth factor. Mol Cell Biol. 1991;11:573-577.
Not in our library10.1128/mcb.11.1.573-577.1991
- 49.
Land T, Rouault TA. Targeting of a human iron-sulfur cluster assembly enzyme, nifs, to different subcellular compartments is regulated through alternative AUG utilization. Mol Cell. 1998;2:807-815.
Not in our library10.1016/s1097-2765(00)80295-6
- 50.
Cai J, Huang Y, Li F, et al. Alteration of protein subcellular location and domain formation by alternative translational initiation. Proteins. 2006;62:793-799.
Not in our library10.1002/prot.20785
- 51.
Pan G, Qin B, Liu N, et al. Identification of a nuclear localization signal in OCT4 and generation of a dominant negative mutant by its ablation. J Biol Chem. 2004;279:37013-37020.
Not in our library10.1074/jbc.m405117200
- 52.
Pesce M, Scholer HR. Oct-4: Gatekeeper in the beginnings of mammalian development. Stem Cells (Dayton, OH). 2001;19:271-278.
Not in our library10.1634/stemcells.19-4-271
- 53.
Kerr CL, Hill CM, Blumenthal PD, et al. Expression of pluripotent stem cell markers in the human fetal testis. Stem Cells (Dayton, OH). 2008;26:412-421.
Not in our library10.1634/stemcells.2007-0605
- 54.
Goto T, Adjaye J, Rodeck CH, et al. Identification of genes expressed in human primordial germ cells at the time of entry of the female germ line into meiosis. Mol Hum Reprod. 1999;5:851-860.
Not in our library10.1093/molehr/5.9.851
- 55.
- 56.
Monk M, Hitchins M, Hawes S. Differential expression of the embryo/cancer gene ECSA(DPPA2), the cancer/testis gene BORIS and the pluripotency structural gene OCT4, in human preimplantation development. Mol Hum Reprod. 2008;14:347-355.
Not in our library10.1093/molehr/gan025
- 57.
Kehler J, Tolkunova E, Koschorz B, et al. Oct4 is required for primordial germ cell survival. EMBO Rep. 2004;5:1078-1083.
Not in our library10.1038/sj.embor.7400279
- 58.
Looijenga LH, Stoop H, de Leeuw HP, et al. POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors. Cancer Res. 2003;63:2244-2250.
Not in our library
- 59.
Rajpert-De Meyts E, Hanstein R, Jorgensen N, et al. Developmental expression of POU5F1 (OCT-3/4) in normal and dysgenetic human gonads. Hum Reprod (Oxford, England). 2004;19:1338-1344.
Not in our library10.1093/humrep/deh265
- 60.
Jones TD, Ulbright TM, Eble JN, et al. OCT4 staining in testicular tumors: A sensitive and specific marker for seminoma and embryonal carcinoma. Am J Surg Pathol. 2004;28:935-940.
Not in our library10.1097/00000478-200407000-00014
- 61.
Cheng L. Establishing a germ cell origin for metastatic tumors using OCT4 immunohistochemistry. Cancer. 2004;101:2006-2010.
Not in our library10.1002/cncr.20566
- 62.
de Jong J, Stoop H, Dohle GR, et al. Diagnostic value of OCT3/4 for pre-invasive and invasive testicular germ cell tumours. J Pathol. 2005;206:242-249.
Not in our library10.1002/path.1766
- 63.
Hattab EM, Tu PH, Wilson JD, et al. OCT4 immunohistochemistry is superior to placental alkaline phosphatase (PLAP) in the diagnosis of central nervous system germinoma. Am J Surg Pathol. 2005;29:368-371.
Not in our library10.1097/01.pas.0000149709.19958.a7
- 64.
Gidekel S, Pizov G, Bergman Y, et al. Oct-3/4 is a dose-dependent oncogenic fate determinant. Cancer Cell. 2003;4:361-370.
Not in our library10.1016/s1535-6108(03)00270-8
- 65.
Cheng L, Sung MT, Cossu-Rocca P, et al. OCT4: Biological functions and clinical applications as a marker of germ cell neoplasia. J Pathol. 2007;211:1-9.
Not in our library10.1002/path.2105
- 66.
Mueller T, Luetzkendorf J, Nerger K, et al. Analysis of OCT4 expression in an extended panel of human tumor cell lines from multiple entities and in human mesenchymal stem cells. Cell Mol Life Sci. 2009;66:495-503.
Not in our library10.1007/s00018-008-8623-z
- 67.
Kaltz N, Funari A, Hippauf S, et al. In vivo osteoprogenitor potency of human stromal cells from different tissues does not correlate with expression of POU5F1 or its pseudogenes. Stem Cells (Dayton, OH). 2008;26:2419-2424.
Not in our library10.1634/stemcells.2008-0304
- 68.
Greco SJ, Liu K, Rameshwar P. Functional similarities among genes regulated by OCT4 in human mesenchymal and embryonic stem cells. Stem Cells (Dayton, OH). 2007;25:3143-3154.
Not in our library10.1634/stemcells.2007-0351
- 69.
Mizuno N, Kosaka M. Novel variants of Oct-3/4 gene expressed in mouse somatic cells. J Biol Chem. 2008;283:30997-31004.
Not in our library10.1074/jbc.m802992200
- 70.
Hochedlinger K, Yamada Y, Beard C, et al. Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell. 2005;121:465-477.
Not in our library10.1016/j.cell.2005.02.018
- 71.
Monsef N, Soller M, Isaksson M, et al. The expression of pluripotency marker Oct 3/4 in prostate cancer and benign prostate hyperplasia. Prostate. 2009;69:909-916.
Not in our library10.1002/pros.20934
- 72.
Monk M, Holding C. Human embryonic genes re-expressed in cancer cells. Oncogene. 2001;20:8085-8091.
Not in our library10.1038/sj.onc.1205088
- 73.
Ezeh UI, Turek PJ, Reijo RA, et al. Human embryonic stem cell genes OCT4, NANOG, STELLAR, and GDF3 are expressed in both seminoma and breast carcinoma. Cancer. 2005;104:2255-2265.
Not in our library10.1002/cncr.21432
- 74.
Atlasi Y, Mowla SJ, Ziaee SA, et al. OCT-4, an embryonic stem cell marker, is highly expressed in bladder cancer. Int J Cancer. 2007;120:1598-1602.
Not in our library10.1002/ijc.22508
- 75.
Cantz T, Key G, Bleidissel M, et al. Absence of OCT4 expression in somatic tumor cell lines. Stem Cells (Dayton, OH). 2008;26:692-697.
Not in our library10.1634/stemcells.2007-0657
- 76.
Pal P, Xi H, Guha S, et al. Common variants in 8q24 are associated with risk for prostate cancer and tumor aggressiveness in men of European ancestry. Prostate. 2009;69:1548-1556.
Not in our library10.1002/pros.20999
- 77.
Kim JB, Greber B, Arauzo-Bravo MJ, et al. Direct reprogramming of human neural stem cells by OCT4. Nature. 2009;461:649-643.
Not in our library10.1038/nature08436
- 78.
Wang J, Rao S, Chu J, et al. A protein interaction network for pluripotency of embryonic stem cells. Nature. 2006;444:364-368.
Not in our library10.1038/nature05284
- 79.
Guenther MG, Levine SS, Boyer LA, et al. A chromatin landmark and transcription initiation at most promoters in human cells. Cell. 2007;130:77-88.
Not in our library10.1016/j.cell.2007.05.042
- 80.
Donohoe ME, Silva SS, Pinter SF, et al. The pluripotency factor Oct4 interacts with Ctcf and also controls X-chromosome pairing and counting. Nature. 2009;460:128-132.
Not in our library10.1038/nature08098
- 81.
Loh YH, Zhang W, Chen X, et al. Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells. Genes Dev. 2007;21:2545-2557.
Not in our library10.1101/gad.1588207
- 82.
Sridharan R, Tchieu J, Mason MJ, et al. Role of the murine reprogramming factors in the induction of pluripotency. Cell. 2009;136:364-377.
Not in our library10.1016/j.cell.2009.01.001
- 83.
Wernig M, Meissner A, Foreman R, et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature. 2007;448:318-324.
Not in our library10.1038/nature05944
- 84.
Meissner A, Wernig M, Jaenisch R. Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. Nat Biotechnol. 2007;25:1177-1181.
Not in our library10.1038/nbt1335
- 85.
Papapetrou EP, Tomishima MJ, Chambers SM, et al. Stoichiometric and temporal requirements of Oct4, Sox2, Klf4, and c-Myc expression for efficient human iPSC induction and differentiation. Proc Natl Acad Sci USA. 2009;106:12759-12764.
Not in our library10.1073/pnas.0904825106
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