Isolation of male germ-line stem cells; influence of GDNF

Hofmann, Marie‐Claude; Braydich‐Stolle, Laura K.; Dym, Martin

doi:10.1016/j.ydbio.2004.12.006

Cited by 296 publications

(288 citation statements)

References 69 publications

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“…Despite previous difficulties in identifying FGFR2 in spermatogonial cells, our demonstration of Fgfr2 expression (Fig. 4) is not surprising, given the requirement of FGF for successful spermatogonial cell culture (32,35,36) and the role of FGF receptors in determining the fate of other stem cell types (37).…”

Section: Discussionmentioning

confidence: 67%

Gain-of-function amino acid substitutions drive positive selection of FGFR2 mutations in human spermatogonia

Goriely

McVean²,

Pelt³

et al. 2005

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

133

107

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Despite the importance of mutation in genetics, there are virtually no experimental data on the occurrence of specific nucleotide substitutions in human gametes. C>G transversions at position 755 of FGF receptor 2 (FGFR2) cause Apert syndrome; this mutation, encoding the gain-of-function substitution Ser252Trp, occurs with a birth rate elevated 200-to 800-fold above background and originates exclusively from the unaffected father. We previously demonstrated high levels of both 755C>G and 755C>T FGFR2 mutations in human sperm and proposed that these particular mutations are enriched because the encoded proteins confer a selective advantage to spermatogonial cells. Here, we examine three corollaries of this hypothesis. First, we show that mutation levels at the adjacent FGFR2 nucleotides 752-754 are low, excluding any general increase in local mutation rate. Second, we present three instances of double-nucleotide changes involving 755C, expected to be extremely rare as chance events. Two of these double-nucleotide substitutions are shown, either by assessment of the pedigree or by direct analysis of sperm, to have arisen in sequential steps; the third (encoding Ser252Tyr) was predicted from structural considerations. Finally, we demonstrate that both major alternative spliceforms of FGFR2 (Fgfr2b and Fgfr2c) are expressed in rat spermatogonial stem cell lines. Taken together, these observations show that specific FGFR2 mutations attain high levels in sperm because they encode proteins with gain-of-function properties, favoring clonal expansion of mutant spermatogonial cells. Among FGFR2 mutations, those causing Apert syndrome may be especially prevalent because they enhance signaling by FGF ligands specific for each of the major expressed isoforms.Apert syndrome ͉ FGF receptor 2 ͉ paternal age ͉ selfish mutation

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Section: Discussionmentioning

confidence: 67%

Gain-of-function amino acid substitutions drive positive selection of FGFR2 mutations in human spermatogonia

Goriely

McVean²,

Pelt³

et al. 2005

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

133

107

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“…Over-expression of GDNF resulted in accumulation of SSCs (Meng et al 2000). GDNF has a positive effect on stem cells maintenance, and was also involved in spermatogonial proliferation and differentiation (Hofmann et al 2005). LIF has an important role in the regulation of spermatogonial cells compartment (Dorval-Coiffec et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Effects of GDNF and LIF on mouse spermatogonial stem cells proliferation in vitro

et al. 2013

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Spermatogonial stem cells (SSCs) are the only type of cells that transmit genes to the subsequent generations. The proliferation, cultivation and identification of SSCs in vitro are critical to understanding of male infertility, genetic resources and conservation of endangered species. To investigate the effects of glial cell-derived neurotrophic factor (GDNF) and leukemia inhibitory factor (LIF) on the proliferation of mouse SSCs in vitro, supplement of GDNF and/or LIF were designed to culture SSCs. The testes of 6-8 d mouse were harvested and digested by two-step enzyme digestion method. The SSCs and Sertoli cells were separated by differential plating. Then the SSCs were identified by alkaline phosphatase staining, RT-PCR and indirect immunofluorescence cell analysis. The cellular proliferation capacity was measured by methyl thiazolyl tetrazolium assay. The results showed that addition of 20 and 40 ng/ml of GDNF could strongly promote growth of mouse SSCs (p \ 0.05). There was no significant difference between LIF treatment groups and the control group in promoting proliferation of the mouse SSCs (p[0.05). However, the combination of 20 ng/ml GDNF and 1,000 U/ml LIF could significantly enhance the invitro proliferation of mouse SSCs (p \ 0.05), and the OD 490 value was 0.696 at day 5 of culture when the density of SSCs was 5-10 9 10 4 cells/ml.

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“…However, a scarce knowledge of molecular markers has been accumulated in recent years (Kokkinaki et al, 2010). Some research groups have demonstrated that glial cell-.derived neurotrophic factor (GDNF) is the most essential factor for SSC self-renewal and in vitro maintenance in rodents (Caires et al, 2010;Ryu et al, 2005;Meng et al, 2000;Kubota et al, 2004a,b;Kanatsu-Shinohara et al, 2005;Kanatsu-Shinohara et al, 2008;and Braydish-Stalle et al, 2005) and that GDNF receptor (GFRA1) is expressed by SSC/progenitor cells (Naughton et al, 2006;Hofmann et al, 2005 andHe et al, 2007). The activation of GDNF pathway probably is related with other pathways that promote the proliferation and the self-renewal of SSCs (Caires et al, 2010;Jijiwa et al, 2004;Braydich-Stolle et al, 2007;Oatley et al, 2007 andLee et al, 2006).…”

Section: Characterization Of Spermatogonial Stem Cellsmentioning

confidence: 99%

“…GDNF is related to neural development (He et al, 2007 andGarces et al, 2000) and renal morphogenesis (He et al, 2007 andVega et al, 1996). In spermatogonial cells, this factor plays an important role in the regulation of proliferation and differentiation or undifferentiated (He et al, 2007, Naughton et al, 2006Takakoro et al, 2002;Meng et al, 2000 andHofmann et al, 2005). Others important markers are Nanog and Pou5f1 (Oct3/4).…”

Section: Ssc Markers and Differences Among Speciesmentioning

confidence: 99%