Plzf is required in adult male germ cells for stem cell self-renewal

Buaas, F. William; Kirsh, Andrew L.; Sharma, Manju; McLean, Derek J.; Morris, Jamie L; Griswold, Michael D.; Rooij, Dirk G. de; Braun, Robert E.

doi:10.1038/ng1366

Cited by 806 publications

(755 citation statements)

References 29 publications

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“…To test whether spermatogonia in our mutant zebrafish testes had abnormal features as reported in mice, we examined the premeiotic spermatogonial populations by examining the expression of Plzf (also known as zfp145), which is known as an undifferentiated spermatogonia-specific transcription factor in the mouse testis and is used as a molecular marker of undifferentiated spermatogonia (Buaas et al, 2004;Costoya et al, 2004). In zebrafish, Plzf is also expressed in type A spermatogonia, defined as a single spermatogonium in a cyst, and early type B spermatogonia, which are spermatogonia within cysts of 8 or fewer spermatogonial cells (Ozaki et al, 2011).…”

Section: Developmental Dynamicsmentioning

confidence: 99%

Isolation and cytogenetic characterization of zebrafish meiotic prophase I mutants

Saito

Siegfried

Nüsslein‐Volhard

et al. 2011

Developmental Dynamics

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We describe here the isolation and cytogenetic characterization of three meiotic prophase I mutants, denoted ietsugu (its), iesada (isa), and iemochi (imo), isolated by a novel N-ethyl-N-nitrosourea mutagenesis screen for adult zebrafish gonadogenesis. Histological examination and flow cytometry analysis of testes from these mutants showed that each contained neither spermatids nor sperm. Staining for Sycp3 and cleaved Caspase-3 and TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling) assay further revealed that its had defects at the onset of meiosis, and that isa and imo spermatocytes failed to progress past the zygotene stage with apoptosis occurring in the testicular somatic cells. Staining for phosphorylated histone H2AX showed that foci formation in leptotene spermatocytes was disrupted in isa and imo. Furthermore, in vitro differentiation experiments revealed the possibility that the defects and sterility associated with mutations were germ line autonomous. Our results thus indicate that each responsible gene is necessary for meiotic progression during spermatogenesis and for male fertility.

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Section: Developmental Dynamicsmentioning

confidence: 99%

Isolation and cytogenetic characterization of zebrafish meiotic prophase I mutants

Saito

Siegfried

Nüsslein‐Volhard

et al. 2011

Developmental Dynamics

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“…Several knockouts targeting transcription factors have recently resulted in mice exhibiting a progressive loss of germ cells leading to adult infertility (Chen et al, 2005;Falender et al, 2005;Buaas et al, 2004;Costoya et al, 2004). One of these factors, Etv5 (Ets Variant Gene 5), belongs to the Pea3 group of the Ets family of proteins, which are characterized by a highly conserved DNA-binding ETS domain (Sharrocks et al, 1997).…”

Section: Etv5 and Other Transcription Factorsmentioning

confidence: 99%

Gdnf signaling pathways within the mammalian spermatogonial stem cell niche

Hofmann

2008

Molecular and Cellular Endocrinology

204

178

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SummaryMammalian spermatogenesis is a complex process in which male germ-line stem cells develop to ultimately form spermatozoa. Spermatogonial stem cells, or SSCs, are found in the basal compartment of the seminiferous epithelium. They self-renew to maintain the pool of stem cells throughout life, or they differentiate to generate a large number of germ cells. A balance between SSC self-renewal and differentiation in the adult testis is therefore essential to maintain normal spermatogenesis and fertility. Maintenance and self-renewal are tightly regulated by extrinsic signals from the surrounding microenvironment, called the spermatogonial stem cell niche. By physically supporting the SSCs and providing them with growth factors, the Sertoli cell is the main component of the niche. In addition, adhesion molecules that connect the SSCs to the basement membrane and cellular components of the interstitium between the seminiferous tubules are important regulators of the niche function. This review mainly focuses on glial cell line-derived neurotrophic factor (Gdnf), which is produced by Sertoli cells to maintain SSCs self-renewal, and the downstream signaling pathways induced by this crucial growth factor. Interactions between Gdnf and other signaling pathways that maintain self-renewal, as well as the role of novel SSC-and Sertoli cell-specific transcription factors, are also discussed.

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“…In the mouse testis, putative stem cells have been selected on the basis of expression of c-Kit and the β1 and α6 integrins [134]. The expression of the transcription factors Oct-4 and Plfz has also been used to define murine testicular stem cells [135], and an SP population (dependent on ABCG2 activity) was found highly-enriched for in vivo cell repopulation ability, with these cells expressing α6 integrin and Stra8, a premeiotic germ cell-specific cytoplasmic protein [136]. In man, as in many primates, there are two types of A spermatogonia; A dark , likely to be facultative stem cells, and A pale , being progenitor cells [137].…”

Section: Male Gonadal and Accessory Sex Tissuementioning

confidence: 99%

Attributes of adult stem cells

Alison

Islam

2008

The Journal of Pathology

153

115

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While cultured embryonic stem (ES) cells can be harvested in abundance and appear to be the most versatile of cells for regenerative medicine, adult stem cells also hold promise, but the identity and subsequent isolation of these comparatively rare cells remains problematic in most tissues, perhaps with the notable exception of the bone marrow. The ability to continuously self-renew and produce the differentiated progeny of the tissue of their location are their defining properties. Identifying surface molecules (markers) that would aid in stem cell isolation is a major goal. Considerable overlap exists between different putative organspecific stem cells in their repertoire of gene expression, often related to self-renewal, cell survival and cell adhesion. More robust tests of 'stemness' are now being employed, using lineage-specific genetic marking and tracking to show production of long-lived clones and multipotentiality in vivo. Moreover, the characterization of normal stem cells in specific tissues may provide a dividend for the treatment of cancer. The successful treatment of neoplastic disease may well require the specific targeting of neoplastic stem cells, cells that may well have many of the characteristics of their normal counterparts.

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Plzf is required in adult male germ cells for stem cell self-renewal

Cited by 806 publications

References 29 publications

Isolation and cytogenetic characterization of zebrafish meiotic prophase I mutants

Isolation and cytogenetic characterization of zebrafish meiotic prophase I mutants

Gdnf signaling pathways within the mammalian spermatogonial stem cell niche

Attributes of adult stem cells

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