Gene Expression Profiling of Rat Spermatogonia and Sertoli Cells Reveals Signaling Pathways from Stem Cells to Niche and Testicular Cancer Cells to Surrounding Stroma

Overview

Journal BMC Genomics

Publisher Biomed Central

Specialty Genetics

Date 2011 Jan 15

PMID 21232125

Citations 9

Authors

Stephan Ryser

Dominique Glauser

Michelle Vigier

Yong Qiang Zhang

Philippe Tachini

Werner Schlegel

Philippe Durand

Irmgard Irminger-Finger

Affiliations

Soon will be listed here.

Abstract

Background: Stem cells and their niches are studied in many systems, but mammalian germ stem cells (GSC) and their niches are still poorly understood. In rat testis, spermatogonia and undifferentiated Sertoli cells proliferate before puberty, but at puberty most spermatogonia enter spermatogenesis, and Sertoli cells differentiate to support this program. Thus, pre-pubertal spermatogonia might possess GSC potential and pre-pubertal Sertoli cells niche functions. We hypothesized that the different stem cell pools at pre-puberty and maturity provide a model for the identification of stem cell and niche-specific genes. We compared the transcript profiles of spermatogonia and Sertoli cells from pre-pubertal and pubertal rats and examined how these related to genes expressed in testicular cancers, which might originate from inappropriate communication between GSCs and Sertoli cells.

Results: The pre-pubertal spermatogonia-specific gene set comprised known stem cell and spermatogonial stem cell (SSC) markers. Similarly, the pre-pubertal Sertoli cell-specific gene set comprised known niche gene transcripts. A large fraction of these specifically enriched transcripts encoded trans-membrane, extra-cellular, and secreted proteins highlighting stem cell to niche communication. Comparing selective gene sets established in this study with published gene expression data of testicular cancers and their stroma, we identified sets expressed genes shared between testicular tumors and pre-pubertal spermatogonia, and tumor stroma and pre-pubertal Sertoli cells with statistic significance.

Conclusions: Our data suggest that SSC and their niche specifically express complementary factors for cell communication and that the same factors might be implicated in the communication between tumor cells and their micro-environment in testicular cancer.

Citing Articles

Germ Cell Neoplasia in Undescended Testis: A Myth or Reality?.

Mishra P, Purkait S, Manekar A, Tripathy B J Indian Assoc Pediatr Surg. 2025; 30(1):66-69.

PMID: 39968261 PMC: 11832094. DOI: 10.4103/jiaps.jiaps_182_24.

Genetic insights into non-obstructive azoospermia: Implications for diagnosis and TESE outcomes.

Sharifi S, Dursun M, Sahin A, Turan S, Altun A, Ozcan O J Assist Reprod Genet. 2025; .

PMID: 39932629 DOI: 10.1007/s10815-025-03409-5.

Super-enhancer switching drives a burst in gene expression at the mitosis-to-meiosis transition.

Maezawa S, Sakashita A, Yukawa M, Chen X, Takahashi K, Alavattam K Nat Struct Mol Biol. 2020; 27(10):978-988.

PMID: 32895557 PMC: 8690596. DOI: 10.1038/s41594-020-0488-3.

Testicular Lmcd1 regulates phagocytosis by Sertoli cells through modulation of NFAT1/Txlna signaling pathway.

Jin X, Zhang S, Ding T, Zhao P, Zhang C, Zhang Y Aging Cell. 2020; 19(10):e13217.

PMID: 32840323 PMC: 7576262. DOI: 10.1111/acel.13217.

RAPID COMMUNICATION: Multi-breed validation study unraveled genomic regions associated with puberty traits segregating across tropically adapted breeds1.

Melo T, Fortes M, Fernandes Junior G, Albuquerque L, Carvalheiro R J Anim Sci. 2019; 97(7):3027-3033.

PMID: 30997484 PMC: 6606496. DOI: 10.1093/jas/skz121.

References

Almstrup K, Hoei-Hansen C, Wirkner U, Blake J, Schwager C, Ansorge W . Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling. Cancer Res. 2004; 64(14):4736-43. DOI: 10.1158/0008-5472.CAN-04-0679. View

Capurro M, Xu P, Shi W, Li F, Jia A, Filmus J . Glypican-3 inhibits Hedgehog signaling during development by competing with patched for Hedgehog binding. Dev Cell. 2008; 14(5):700-11. DOI: 10.1016/j.devcel.2008.03.006. View

Nakagawa T, Nabeshima Y, Yoshida S . Functional identification of the actual and potential stem cell compartments in mouse spermatogenesis. Dev Cell. 2007; 12(2):195-206. DOI: 10.1016/j.devcel.2007.01.002. View

Griswold M . The central role of Sertoli cells in spermatogenesis. Semin Cell Dev Biol. 1998; 9(4):411-6. DOI: 10.1006/scdb.1998.0203. View

Wu J, Jester Jr W, Orth J . Short-type PB-cadherin promotes survival of gonocytes and activates JAK-STAT signalling. Dev Biol. 2005; 284(2):437-50. DOI: 10.1016/j.ydbio.2005.05.042. View

de Rooij D . Proliferation and differentiation of spermatogonial stem cells. Reproduction. 2001; 121(3):347-54. DOI: 10.1530/rep.0.1210347. View

Brehm R, Steger K . Regulation of Sertoli cell and germ cell differentation. Adv Anat Embryol Cell Biol. 2005; 181:1-93. View

Hoei-Hansen C, Nielsen J, Almstrup K, Hansen M, Skakkebaek N, Rajpert-DeMeyts E . Identification of genes differentially expressed in testes containing carcinoma in situ. Mol Hum Reprod. 2004; 10(6):423-31. DOI: 10.1093/molehr/gah059. View

Griswold M . Interactions between germ cells and Sertoli cells in the testis. Biol Reprod. 1995; 52(2):211-6. DOI: 10.1095/biolreprod52.2.211. View

10.

Dar A, Goichberg P, Shinder V, Kalinkovich A, Kollet O, Netzer N . Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells. Nat Immunol. 2005; 6(10):1038-46. DOI: 10.1038/ni1251. View

11.

Braydich-Stolle L, Kostereva N, Dym M, Hofmann M . Role of Src family kinases and N-Myc in spermatogonial stem cell proliferation. Dev Biol. 2007; 304(1):34-45. PMC: 2077853. DOI: 10.1016/j.ydbio.2006.12.013. View

12.

Fouchecourt S, Godet M, Sabido O, Durand P . Glial cell-line-derived neurotropic factor and its receptors are expressed by germinal and somatic cells of the rat testis. J Endocrinol. 2006; 190(1):59-71. DOI: 10.1677/joe.1.06699. View

13.

Yoshida S, Sukeno M, Nabeshima Y . A vasculature-associated niche for undifferentiated spermatogonia in the mouse testis. Science. 2007; 317(5845):1722-6. DOI: 10.1126/science.1144885. View

14.

Shima J, McLean D, McCarrey J, Griswold M . The murine testicular transcriptome: characterizing gene expression in the testis during the progression of spermatogenesis. Biol Reprod. 2004; 71(1):319-30. DOI: 10.1095/biolreprod.103.026880. View

15.

Brehm R, Ruttinger C, Fischer P, Gashaw I, Winterhager E, Kliesch S . Transition from preinvasive carcinoma in situ to seminoma is accompanied by a reduction of connexin 43 expression in Sertoli cells and germ cells. Neoplasia. 2006; 8(6):499-509. PMC: 1601470. DOI: 10.1593/neo.05847. View

16.

Oosterhuis J, Looijenga L . Testicular germ-cell tumours in a broader perspective. Nat Rev Cancer. 2005; 5(3):210-22. DOI: 10.1038/nrc1568. View

17.

Shinohara T, Orwig K, Avarbock M, Brinster R . Remodeling of the postnatal mouse testis is accompanied by dramatic changes in stem cell number and niche accessibility. Proc Natl Acad Sci U S A. 2001; 98(11):6186-91. PMC: 33443. DOI: 10.1073/pnas.111158198. View

18.

Dettin L, Ravindranath N, Hofmann M, Dym M . Morphological characterization of the spermatogonial subtypes in the neonatal mouse testis. Biol Reprod. 2003; 69(5):1565-71. DOI: 10.1095/biolreprod.103.016394. View

19.

Weiss M, Vigier M, Hue D, Marret C, Avallet O, Durand P . Pre- and postmeiotic expression of male germ cell-specific genes throughout 2-week cocultures of rat germinal and Sertoli cells. Biol Reprod. 1997; 57(1):68-76. DOI: 10.1095/biolreprod57.1.68. View

20.

Wadham C, Gamble J, Vadas M, Khew-Goodall Y . The protein tyrosine phosphatase Pez is a major phosphatase of adherens junctions and dephosphorylates beta-catenin. Mol Biol Cell. 2003; 14(6):2520-9. PMC: 194899. DOI: 10.1091/mbc.e02-09-0577. View