Wnt signaling promotes proliferation and stemness regulation of spermatogonial stem/progenitor cells.
Spermatogonial stem cells (SSCs) self-renew throughout life to produce progenitor cells that are able to differentiate into spermatozoa. However, the mechanisms underlying the cell fate determination between self-renewal and differentiation have not yet been delineated. Culture conditions and growth factors essential for self-renewal and proliferation of mouse SSCs have been investigated, but no information is available related to growth factors that affect fate determination of human spermatogonia. Wnts form a large family of secreted glycoproteins, the members of which are involved in cell proliferation, differentiation, organogenesis, and cell migration. Here, we show that Wnts and their receptors Fzs are expressed in mouse spermatogonia and in the C18-4 SSC line. We demonstrate that WNT3A induces cell proliferation, morphological changes, and cell migration in C18-4 cells. Furthermore, we show that beta-catenin is activated during testis development in 21-day-old mice. In addition, our study demonstrates that WNT3A sustained adult human embryonic stem (ES)-like cells derived from human germ cells in an undifferentiated stage, expressing essential human ES cell transcription factors. These results demonstrate for the first time that Wnt/beta-catenin pathways, especially WNT3A, may play an important role in the regulation of mouse and human spermatogonia.
Departments of, Biochemistry and Molecular and Cellular Biology Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3900 Reservoir Road, Northwest, Washington, District of Columbia 20057, USA.
Nady
N
Golestaneh
Elspeth
E
Beauchamp
Shannon
S
Fallen
Maria
M
Kokkinaki
Aykut
A
Uren
Martin
M
Dym
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D000072261:Dishevelled Proteins; D051157:Frizzled Receptors / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D013093:Spermatogonia / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism*; D060509:Wnt3A Protein / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C495267:CTNNB1 protein, mouse; D017077:Culture Media, Conditioned; D000072261:Dishevelled Proteins; D051157:Frizzled Receptors; D010750:Phosphoproteins; C555510:WNT3A protein, human; D051153:Wnt Proteins; C102068:Wnt10b protein, mouse; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D051176:beta Catenin