OCT4 and downstream factors are expressed in human somatic urogenital epithelia and in culture of epididymal spheres

被引:30
作者
Kristensen, David M. [1 ]
Nielsen, John E. [1 ]
Kalisz, Mark [2 ]
Dalgaard, Marlene D. [1 ]
Audouze, Karine [3 ]
Larsen, Malene E. [3 ]
Jacobsen, Grete K. [5 ]
Horn, Thomas [4 ]
Brunak, Soren [3 ]
Skakkebaek, Niels E. [1 ]
Leffers, Henrik [1 ]
机构
[1] Rigshosp, Univ Dept Growth & Reprod, Sect GR5064, DK-2100 Copenhagen, Denmark
[2] Hagedorn Res Inst, DK-2820 Gentofte, Denmark
[3] Tech Univ Denmark, Ctr Biol Sequence Anal, Dept Syst Biol, DK-2800 Lyngby, Denmark
[4] Herlev Hosp, Dept Pathol, DK-2730 Herlev, Denmark
[5] Rigshosp, Dept Pathol, DK-2100 Copenhagen, Denmark
关键词
OCT4; epididymis; prostate; CD133; epididymal sphere; EMBRYONIC STEM-CELLS; GENE-EXPRESSION; EPIGENETIC CONTROL; SELF-RENEWAL; OCT-3/4; DIFFERENTIATION; PLURIPOTENT; NANOG; TUMOR; REX-1;
D O I
10.1093/molehr/gaq008
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The transcription factor OCT4 plays a crucial role in the earliest differentiation of the mammalian embryo and in self-renewal of embryonic stem cells. However, it remains controversial whether this gene is also expressed in somatic tissues. Here, we use a combination of RT-PCR on whole and microdissected tissues, in situ hybridization, immunohistochemistry and western blotting to show that OCT4 and SOX2 together with downstream targets, UTF1 and REX1/ZFP42, are expressed in the human male urogenital tract. We further support these results by the analysis of DNA methylation of a region in the OCT4 promoter. In culture, human primary epididymal cells formed spheres that continued to express the investigated genes for at least 20 days. Transcriptomic analysis of cultured cells showed up-regulation of CD29, CD44 and CD133 that are normally associated with sphere-forming cancer stem cells. Furthermore, stimulation with retinoic acid resulted in down-regulation of OCT4 expression, however, without multilineage differentiation. Our results show that OCT4 and associated genes are expressed in somatic epithelial cells from the urogenital tract and that these cells can form spheres, a general marker of stem cell behaviour.
引用
收藏
页码:835 / 845
页数:11
相关论文
共 36 条
[1]   Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling [J].
Almstrup, K ;
Hoei-Hansen, CE ;
Wirkner, U ;
Blake, J ;
Schwager, C ;
Ansorge, W ;
Nielsen, JE ;
Skakkebæk, NE ;
Meyts, ERD ;
Leffers, H .
CANCER RESEARCH, 2004, 64 (14) :4736-4743
[2]   A meta-analysis of human embryonic stem cells transcriptome integrated into a web-based expression atlas [J].
Assou, Said ;
Le Carrour, Tanguy ;
Tondeur, Sylvie ;
Strom, Susanne ;
Gabelle, Audrey ;
Marty, Sophie ;
Nadal, Laure ;
Pantesco, Veronique ;
Reme, Thierry ;
Hugnot, Jean-Philippe ;
Gasca, Stephan ;
Hovatta, Outi ;
Hamamah, Samir ;
Klein, Bernard ;
De Vos, John .
STEM CELLS, 2007, 25 (04) :961-973
[3]   OCT4 Spliced Variants Are Differentially Expressed in Human Pluripotent and Nonpluripotent Cells [J].
Atlasi, Yaser ;
Mowla, Seyed J. ;
Ziaee, Seyed A. M. ;
Gokhale, Paul J. ;
Andrews, Peter W. .
STEM CELLS, 2008, 26 (12) :3068-3074
[4]   Gli activity correlates with tumor grade in platelet-derived growth factor-induced gliomas [J].
Becher, Oren J. ;
Hambardzumyan, Dolores ;
Fomehenko, Elena I. ;
Momota, Hiroyuki ;
Mainwaring, Lori ;
Bleau, Anne-Marie ;
Katz, Amanda M. ;
Edgar, Mark ;
Kenney, Anna M. ;
Cordon-Cardo, Carlos ;
Blasberg, Ron G. ;
Holland, Eric C. .
CANCER RESEARCH, 2008, 68 (07) :2241-2249
[5]   Rex-1, a gene encoding a transcription factor expressed in rbe early embryo, is regulated via Oct-3/4 and Oct-6 binding to an Octamer site and a novel protein, Rox-1, binding to an adjacent site [J].
Ben-Shushan, E ;
Thompson, JR ;
Gudas, LJ ;
Bergman, Y .
MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (04) :1866-1878
[6]   Eleven daughters of NANOG [J].
Booth, HAF ;
Holland, PWH .
GENOMICS, 2004, 84 (02) :229-238
[7]   Core transcriptional regulatory circuitry in human embryonic stem cells [J].
Boyer, LA ;
Lee, TI ;
Cole, MF ;
Johnstone, SE ;
Levine, SS ;
Zucker, JR ;
Guenther, MG ;
Kumar, RM ;
Murray, HL ;
Jenner, RG ;
Gifford, DK ;
Melton, DA ;
Jaenisch, R ;
Young, RA .
CELL, 2005, 122 (06) :947-956
[8]   Absence of OCT4 expression in somatic tumor cell lines [J].
Cantz, Tobias ;
Key, Goeran ;
Bleidissel, Martina ;
Gentile, Luca ;
Han, Dong Wook ;
Brenne, Alexandra ;
Schoeler, Hans R. .
STEM CELLS, 2008, 26 (03) :692-697
[9]   RETRACTED: Generation of pluripotent stem cells from adult human testis (Retracted article. See vol. 512, pg. 338, 2014) [J].
Conrad, Sabine ;
Renninger, Markus ;
Hennenlotter, Joerg ;
Wiesner, Tina ;
Just, Lothar ;
Bonin, Michael ;
Aicher, Wilhelm ;
Buehring, Hans-Joerg ;
Mattheus, Ulrich ;
Mack, Andreas ;
Wagner, Hans-Joachim ;
Minger, Stephen ;
Matzkies, Matthias ;
Reppel, Michael ;
Hescheler, Juergen ;
Sievert, Karl-Dietrich ;
Stenzl, Arnulf ;
Skutella, Thomas .
NATURE, 2008, 456 (7220) :344-U25
[10]   Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells [J].
Cowan, CA ;
Atienza, J ;
Melton, DA ;
Eggan, K .
SCIENCE, 2005, 309 (5739) :1369-1373