title: Newer insights into premeiotic development of germ cells in adult human testis using Oct-4 as a stem cell marker.
abstract: The transcription factor octamer-binding transforming factor 4 (Oct-4) is central to the gene regulatory network responsible for self-renewal, pluripotency, and lineage commitment in embryonic stem (ES) cells and induced pluripotent stem cells (PSCs). This study was undertaken to evaluate differential localization and expression of two major transcripts of Oct-4, viz. Oct-4A and Oct-4B, in adult human testis. A novel population of 5- to 10-μm PSCs with nuclear Oct-4A was identified by ISH and immunolocalization studies. Besides Oct-4, other pluripotent markers like Nanog and TERT were also detected by RT-PCR. A(dark) spermatogonial stem cells (SSCs) were visualized in pairs and chains undergoing clonal expansion and stained positive for cytoplasmic Oct-4B. Quantitative PCR and Western blotting revealed both the transcripts, with higher expression of Oct-4B. It is proposed that PSCs undergo asymmetric cell division and give rise to A(dark) SSCs, which proliferate and initiate lineage-specific differentiation. The darkly stained nuclei in A(dark) SSCs may represent extensive nuclear reprogramming by epigenetic changes when a PSC becomes committed. Oct-4B eventually disappeared in mature germ cells, viz. spermatocytes, spermatids, and sperm. Besides maintaining normal testicular homeostasis, PSCs may also be implicated in germ cell tumors and ES-like colonies that have recently been derived from adult human testicular tissue.
authors.affiliation: Dept. of Stem Cell Biology, National Institute for Research in Reproductive Health, JM Street, Parel, Mumbai 400012, India. deepa.bhartiya@yahoo.in
authors.forename: Deepa
authors.initials: D
authors.lastname: Bhartiya
authors.forename: Sandhya
authors.initials: S
authors.lastname: Kasiviswanathan
authors.forename: Sreepoorna K
authors.initials: SK
authors.lastname: Unni
authors.forename: Prasad
authors.initials: P
authors.lastname: Pethe
authors.forename: Jayesh V
authors.initials: JV
authors.lastname: Dhabalia
authors.forename: Sujata
authors.initials: S
authors.lastname: Patwardhan
authors.forename: Hemant B
authors.initials: HB
authors.lastname: Tongaonkar
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008540:Meiosis; D008875:Middle Aged; D050814:Octamer Transcription Factor-3 / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000601:surgery; D013093:Spermatogonia / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013737:Testis / Q000166:cytology* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D050814:Octamer Transcription Factor-3
references.citation: Cell Stem Cell. 2007 Oct 11;1(4):364-6
references.pmid: 18371374
references.citation: Nature. 1970 Aug 15;227(5259):680-5
references.pmid: 5432063
references.citation: Stem Cells. 2008 Jan;26(1):290-1
references.pmid: 17932416
references.citation: Stem Cell Rev Rep. 2010 Jun;6(2):307-16
references.pmid: 20309650
references.citation: Stem Cells. 2007 Jul;25(7):1675-80
references.pmid: 17379765
references.citation: Stem Cells. 2009 Jun;27(6):1265-75
references.pmid: 19489092
references.citation: J Biol Chem. 2006 Nov 3;281(44):33554-65
references.pmid: 16951404
references.citation: Nat Genet. 2000 Apr;24(4):372-6
references.pmid: 10742100
references.citation: Ann Oncol. 2005 Jun;16(6):863-8
references.pmid: 15821122
references.citation: Dev Biol. 2003 Jun 1;258(1):209-25
references.pmid: 12781694
references.citation: Reproduction. 2006 Nov;132(5):673-80
references.pmid: 17071768
references.citation: Stem Cells. 2008 Dec;26(12):3068-74
references.pmid: 18787205
references.citation: Hum Reprod Update. 2006 May-Jun;12(3):275-82
references.pmid: 16446319
references.citation: PLoS One. 2007 Jun 20;2(6):e553
references.pmid: 17579724
references.citation: Nature. 2006 Apr 27;440(7088):1199-203
references.pmid: 16565704
references.citation: Dev Biol. 2005 Mar 1;279(1):114-24
references.pmid: 15708562
references.citation: Stem Cells Dev. 2009 Apr;18(3):435-45
references.pmid: 18699724
references.citation: J Histochem Cytochem. 2009 Sep;57(9):861-9
references.pmid: 19435714
references.citation: J Histochem Cytochem. 1981 Jul;29(7):844-50
references.pmid: 6167611
references.citation: Nucleic Acids Res. 1992 Sep 11;20(17):4613-20
references.pmid: 1408763
references.citation: Arch Histol Cytol. 2004 Nov;67(4):285-96
references.pmid: 15700536
references.citation: Clin Cancer Res. 2004 Dec 15;10(24):8544-7
references.pmid: 15623637
references.citation: Cytometry A. 2009 Jan;75(1):4-13
references.pmid: 18988270
references.citation: Cell Cycle. 2008 Mar 15;7(6):725-8
references.pmid: 18239456
references.citation: Aging (Albany NY). 2010 Jan 26;2(1):3-6
references.pmid: 20228938
references.citation: Nat Rev Cancer. 2007 Apr;7(4):246-55
references.pmid: 17384580
references.citation: Hum Reprod. 2001 Aug;16(8):1575-82
references.pmid: 11473945
references.citation: J Androl. 2000 Nov-Dec;21(6):776-98
references.pmid: 11105904
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4093-8
references.pmid: 18326628
references.citation: Cold Spring Harb Symp Quant Biol. 2008;73:17-23
references.pmid: 19022768
references.citation: Stem Cells Dev. 2009 Oct;18(8):1115-26
references.pmid: 19281326
references.citation: Am J Anat. 1966 Mar;118(2):509-24
references.pmid: 5917196
references.citation: Stem Cells. 2009 Jan;27(1):138-49
references.pmid: 18927477
references.citation: N Engl J Med. 1997 Jul 24;337(4):242-53
references.pmid: 9227931
references.citation: Reprod Med Biol. 2009 Apr 28;8(2):71-77
references.pmid: 29699310
references.citation: Nature. 2007 Sep 20;449(7160):346-50
references.pmid: 17882221
references.citation: Physiol Rev. 1972 Jan;52(1):198-236
references.pmid: 4621362
references.citation: Birth Defects Res C Embryo Today. 2009 Mar;87(1):27-34
references.pmid: 19306345
references.citation: Reproduction. 2010 Mar;139(3):479-93
references.pmid: 19880674
references.citation: Fertil Steril. 1966 Nov-Dec;17(6):705-21
references.pmid: 5920556
references.citation: Stem Cells. 2001;19(4):271-8
references.pmid: 11463946
references.citation: Cancer Res. 2003 May 1;63(9):2244-50
references.pmid: 12727846
references.citation: J Cell Physiol. 2009 Apr;219(1):1-7
references.pmid: 19097034
references.citation: Biol Reprod. 2010 Feb;82(2):363-72
references.pmid: 19846602
references.citation: Folia Histochem Cytobiol. 2005;43(4):175-81
references.pmid: 16382880
references.citation: Bull Hist Med. 1978 Summer;52(2):162-82
references.pmid: 361110
references.citation: Nature. 2008 Nov 20;456(7220):344-9
references.pmid: 18849962
references.citation: Hum Reprod. 2004 Jun;19(6):1338-44
references.pmid: 15105401
references.citation: Hum Reprod. 2010 Jan;25(1):158-67
references.pmid: 19815622
references.citation: Stem Cells. 2010 May;28(5):885-93
references.pmid: 20333750
references.citation: Biochem Soc Trans. 2005 Dec;33(Pt 6):1526-30
references.pmid: 16246161
references.citation: Biol Chem. 2008 Jul;389(7):845-50
references.pmid: 18627312
references.citation: Hum Reprod. 2008 Apr;23(4):775-82
references.pmid: 18281244