Expression of the homophilic adhesion molecule, Ep-CAM, in the mammalian germ line

Anderson, Rebecca Cogwell; Schaible, Kyle; Heasman, Janet; Wylie, Chris

doi:10.1530/jrf.0.1160379

Cited by 94 publications

(74 citation statements)

References 4 publications

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“…PGS4 and pGS6 expressed PLZF at higher levels than whole neonate testis (Table 1). EPCAM is a homophilic adhesion molecule expressed by undifferentiated germ cells and ES cells (Anderson et al 1999), and indeed Epcam expression has also been reported in mouse SSCs (Kanatsu- Shinohara et al 2004). EPCAM expression levels were higher in pGS4 and pGS6 than in whole neonate testis (Table 1).…”

Section: In Vitro-cultured Porcine Testicular Cellsmentioning

confidence: 76%

The effects of growth factors on in vitro-cultured porcine testicular cells

Kuijk¹,

Colenbrander²

2009

Reproduction

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Cell lines from neonate porcine testis were cultured and characterized and the effect of growth factors were investigated, in order to determine the requirements for the establishment of porcine male germ cell lines. In primary cultures, three different colony types with distinctive morphologies could be recognized. From colonies resembling mouse spermatogonial stem cells (SSCs), two cell lines were derived and maintained for nine passages after which proliferation stopped. Growth of these cell lines depended on the growth factors leukemia inhibitory factor (LIF), epidermal growth factor (EGF), glial derived neurotrophic factor (GDNF), and fibroblast growth factor (FGF). In both cell lines NANOG, promyelocytic leukemia zinc-finger (PLZF), and EPCAM, were expressed at higher levels and GFRA1, ITGA6, and THY1 at lower levels than in neonate porcine testis. Primary cultures of neonate pig testis were subjected to a factorial design of the growth factors LIF, GDNF, EGF, and FGF. EGF and FGF had a positive effect on the number and size of the SSC-like colonies. Addition of EGF and FGF to primary cell cultures of neonate pig testis affected the expression of NANOG, PLZF, POU5F1, and GATA4, whereas effects of LIF or GDNF could not be detected. FGF decreased the expression levels of NANOG, a marker for pluripotency also expressed in neonatal porcine male germ cells. FGF decreased expression of PLZF and enhanced the expression of pluripotency-related gene POU5F1 and Sertoli cell marker GATA4. EGF had a positive effect on PLZF expression levels and counteracted the positive effect of FGF on GATA4 expression. These results suggest that FGF can impede successful derivation of porcine SSCs from neonate pig testis.

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Section: In Vitro-cultured Porcine Testicular Cellsmentioning

confidence: 76%

The effects of growth factors on in vitro-cultured porcine testicular cells

Kuijk¹,

Colenbrander²

2009

Reproduction

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“…S2E). In addition, sections of testes from 2-wk-old WT, Het, and cKO mice were immunostained with antibodies to GATA4, a marker for Sertoli cells, and to KI67 (Table S1), a marker for cell proliferation (27)(28)(29). All tubules in WT and Het mice contained KI67-labeled germ cells, whereas some tubules in cKO mice lacked KI67-labeled germ cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

Targeting theGdnfGene in peritubular myoid cells disrupts undifferentiated spermatogonial cell development

Chen

Willis

Eddy

2016

Proc. Natl. Acad. Sci. U.S.A.

154

128

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Spermatogonial stem cells (SSCs) are a subpopulation of undifferentiated spermatogonia located in a niche at the base of the seminiferous epithelium delimited by Sertoli cells and peritubular myoid (PM) cells. SSCs self-renew or differentiate into spermatogonia that proliferate to give rise to spermatocytes and maintain spermatogenesis. Glial cell line-derived neurotrophic factor (GDNF) is essential for this process. Sertoli cells produce GDNF and other growth factors and are commonly thought to be responsible for regulating SSC development, but limited attention has been paid to the role of PM cells in this process. A conditional knockout (cKO) of the androgen receptor gene in PM cells resulted in male infertility. We found that testosterone (T) induces GDNF expression in mouse PM cells in vitro and neonatal spermatogonia (including SSCs) co-cultured with T-treated PM cells were able to colonize testes of germ cell-depleted mice after transplantation. This strongly suggested that T-regulated production of GDNF by PM cells is required for spermatogonial development, but PM cells might produce other factors in vitro that are responsible. In this study, we tested the hypothesis that production of GDNF by PM cells is essential for spermatogonial development by generating mice with a cKO of the Gdnf gene in PM cells. The cKO males sired up to two litters but became infertile due to collapse of spermatogenesis and loss of undifferentiated spermatogonia. These studies show for the first time, to our knowledge, that the production of GDNF by PM cells is essential for undifferentiated spermatogonial cell development in vivo.spermatogonial stem cell | stem cell niche | male fertility | spermatogenesis | conditional gene targeting T he seminiferous epithelium is separated by tight junctions between Sertoli cells into a luminal compartment containing spermatocytes and spermatids and a basal compartment containing spermatogonial stem cells (SSCs) and spermatogonia. The basal compartment is bounded above and on the sides by Sertoli cells and below by the basement membrane of the seminiferous tubule and a layer of peritubular myoid (PM) cells. SSCs are thought to reside in a microenvironmental niche in the basal compartment, where extrinsic cues influence their decision to either self-renew or enter the pathway of spermatogonial development (1, 2). They are a minor fraction of the undifferentiated spermatogonia in the basal compartment. The other undifferentiated spermatogonia (progenitors) give rise to differentiating spermatogonia that proliferate mitotically to progress on a developmental pathway toward becoming spermatocytes (3, 4). Our current understanding of the progression of SSCs to differentiating spermatogonia comes mainly from cell kinetic studies, germ cell transplantation assays, and the use of molecular markers that identify different populations of spermatogonia.The leading model for spermatogonial development specifies that when SSCs divide, they either self-renew by becoming two type A-single (A s ) spermato...

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“…The expression of genes for four surface protein markers found on SSCs was significantly enriched in the germ cell populations. In mice, EPCAM has previously been identified on neonatal male germ cells and in adult testes only on spermatogonia (38). In rat, EPCAM is an excellent, and perhaps the best, surface antigen for enrichment of rat gonocytes and SSCs of pups (8).…”

Section: Discussionmentioning

confidence: 99%

Prepubertal human spermatogonia and mouse gonocytes share conserved gene expression of germline stem cell regulatory molecules

Schmidt

Avarbock

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

182

145

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In the human testis, beginning at Ϸ2 months of age, gonocytes are replaced by adult dark (Ad) and pale (Ap) spermatogonia that make up the spermatogonial stem cell (SSC) pool. In mice, the SSC pool arises from gonocytes Ϸ6 days after birth. During puberty in both species, complete spermatogenesis is established by cells that differentiate from SSCs. Essentially pure populations of prepubertal human spermatogonia and mouse gonocytes were selected from testis biopsies and validated by confirming the presence of specific marker proteins in cells. Stem cell potential of germ cells was demonstrated by transplantation to mouse testes, following which the cells migrated to the basement membrane of the seminiferous tubule and were maintained similar to SSCs. Differential gene expression profiles generated between germ cells and testis somatic cells demonstrated that expression of genes previously identified as SSC and spermatogonial-specific markers (e.g., zinc-finger and BTB-domain containing 16, ZBTB16) was greatly elevated in both human spermatogonia and mouse gonocytes compared to somatic cells. Several genes were expressed at significantly higher levels in germ cells of both species. Most importantly, genes known to be essential for mouse SSC self-renewal (e.g., Ret proto-oncogene, Ret; GDNF-family receptor ␣1, Gfr␣1; and B-cell CLL/lymphoma 6, member B, Bcl6b) were more highly expressed in both prepubertal human spermatogonia and mouse gonocytes than in somatic cells. The results indicate remarkable conservation of gene expression, notably for self-renewal genes, in these prepubertal germline cells between two species that diverged phylogenetically Ϸ75 million years ago. mouse spermatogonia ͉ spermatogenesis

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Expression of the homophilic adhesion molecule, Ep-CAM, in the mammalian germ line

Cited by 94 publications

References 4 publications

The effects of growth factors on in vitro-cultured porcine testicular cells

The effects of growth factors on in vitro-cultured porcine testicular cells

Targeting theGdnfGene in peritubular myoid cells disrupts undifferentiated spermatogonial cell development

Prepubertal human spermatogonia and mouse gonocytes share conserved gene expression of germline stem cell regulatory molecules

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