Newer insights into premeiotic development of germ cells in adult human testis using Oct-4 as a stem cell marker.
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.
Bhartiya
Deepa
D
Dept. of Stem Cell Biology, National Institute for Research in Reproductive Health, JM Street, Parel, Mumbai 400012, India. deepa.bhartiya@yahoo.in
Kasiviswanathan
Sandhya
S
Unni
Sreepoorna K
SK
Pethe
Prasad
P
Dhabalia
Jayesh V
JV
Patwardhan
Sujata
S
Tongaonkar
Hemant B
HB
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
D014408:Biomarkers, Tumor; D050814:Octamer Transcription Factor-3
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