Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma <i>in situ</i> and germ cell tumours

Hoei‐Hansen, Christina E.; Almstrup, Kristian; Nielsen, John; Sonne, Si Brask; Græm, Niels; Skakkebæk, Niels E.; Leffers, Henrik; Meyts, Ewa Rajpert‐De

doi:10.1111/j.1365-2559.2005.02182.x

Cited by 200 publications

(158 citation statements)

References 34 publications

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“…Postnatally, the expression of NANOG persisted in marmosets until the neonatal period, whereas individual OCT4+ and TFAP2C+ cells were observed until 6 weeks after birth (Mitchell et al, 2008). These findings are in agreement with a previous report indicating that downregulation of NANOG precedes that of OCT4 (Hoei-Hansen et al, 2005). Histological evaluation of neonatal human testes revealed comparable OCT4 expression pattern (Mitchell et al, 2008;Reijpert-de Meyts et al, 2004).…”

Section: Comparative Expression Analysis In Primordial and Perinatal supporting

confidence: 91%

Male germline stem cells in non-human primates

Sharma¹,

Portela

Langenstroth-Röwer³

et al. 2017

Primate Biol.

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Abstract.Over the past few decades, several studies have attempted to decipher the biology of mammalian germline stem cells (GSCs). These studies provide evidence that regulatory mechanisms for germ cell specification and migration are evolutionarily conserved across species. The characteristics and functions of primate GSCs are highly distinct from rodent species; therefore the findings from rodent models cannot be extrapolated to primates. Due to limited availability of human embryonic and testicular samples for research purposes, two non-human primate models (marmoset and macaque monkeys) are extensively employed to understand human germline development and differentiation. This review provides a broader introduction to the in vivo and in vitro germline stem cell terminology from primordial to differentiating germ cells. Primordial germ cells (PGCs) are the most immature germ cells colonizing the gonad prior to sex differentiation into testes or ovaries. PGC specification and migratory patterns among different primate species are compared in the review. It also reports the distinctions and similarities in expression patterns of pluripotency markers (OCT4A, NANOG, SALL4 and LIN28) during embryonic developmental stages, among marmosets, macaques and humans. This review presents a comparative summary with immunohistochemical and molecular evidence of germ cell marker expression patterns during postnatal developmental stages, among humans and non-human primates. Furthermore, it reports findings from the recent literature investigating the plasticity behavior of germ cells and stem cells in other organs of humans and monkeys. The use of non-human primate models would enable bridging the knowledge gap in primate GSC research and understanding the mechanisms involved in germline development. Reported similarities in regulatory mechanisms and germ cell expression profile in primates demonstrate the preclinical significance of monkey models for development of human fertility preservation strategies.

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Section: Comparative Expression Analysis In Primordial and Perinatal supporting

confidence: 91%

Male germline stem cells in non-human primates

Sharma¹,

Portela

Langenstroth-Röwer³

et al. 2017

Primate Biol.

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“…Ectopic expression of Nanog leads to dedifferentiation and blocks further developmental processes (Taranger et al, 2005). Malignant transformation of teratocarcinomas and germline tumors are caused by ectopic expression of Nanog (Almstrup et al, 2004;Hoei-Hansen et al, 2005;Skotheim et al, 2005). Overexpression of the full-length retrogene Nanog P8 has been identified in a large variety of different solid tumors or cancer cell lines .…”

Section: Discussionmentioning

confidence: 99%

Combined effects of the two reciprocal t(4;11) fusion proteins MLL·AF4 and AF4·MLL confer resistance to apoptosis, cell cycling capacity and growth transformation

et al. 2006

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The reciprocal chromosomal translocation t(4;11) is correlated with infant, childhood, adult and therapyrelated high-risk acute leukemia. Here, we investigated the biological effects of MLL . AF4, AF4 . MLL or the combination of both reciprocal fusion proteins in a conditional in vitro cell culture model system. Several parameters like cell growth, cell cycling capacity, apoptotic behavior and growth transformation were investigated under physiological and stress conditions. Co-transfected cells displayed the highest resistance against apoptotic triggers, cell cycling capacity and lossof-contact inhibition. These analyses were complemented by gene expression profiling experiments and specific gene signatures were established for each of the three cell lines. Interestingly, co-transfected cells strongly upregulate the homeobox gene Nanog. In combination with Oct4, the Nanog homeoprotein is steering maintenance of pluripotency and self-renewal in embryonic stem cells. Transcription of Nanog and other stem cell factors, like Oct4 and Bmi1, was verified in biopsy material of t(4;11) patient cells which express both reciprocal t(4;11) fusion genes. In conclusion, the presence of both reciprocal MLL fusion proteins confers biological properties known from t(4;11) leukemia, suggesting that each of the two fusion proteins contribute specific properties and, in combination, also synergistic effects to the leukemic phenotype.

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“…However, most of these studies focused on pluripotency genes that were also retained in carcinoma in situ and TGCTs. Typical examples are the transcription factors NANOG, OCT4, TFAP2C (AP2g), and the miRNA-binding protein LIN28A, which are expressed not only in rodent and human fetal PGCs and gonocytes (Culty 2009, Weber et al 2010, but also in testicular tumors (Hoei-Hansen et al 2005, Rajpert-De Meyts 2006, Sonne et al 2009, Gillis et al 2011, Aeckerle et al 2012. In mouse and human ESCs, both NANOG and OCT4 were found to belong to a protein network regulating cell pluripotency, which included also Wnt and its downstream target b-catenin (AbuRemaileh et al 2010, Marucci et al 2014.…”

Section: Insights From Non-rodent Speciesmentioning

confidence: 99%

Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges

Manku¹,

Culty²

2015

Reproduction

127

105

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The production of spermatozoa relies on a pool of spermatogonial stem cells (SSCs), formed in infancy from the differentiation of their precursor cells, the gonocytes. Throughout adult life, SSCs will either self-renew or differentiate, in order to maintain a stem cell reserve while providing cells to the spermatogenic cycle. By contrast, gonocytes represent a transient and finite phase of development leading to the formation of SSCs or spermatogonia of the first spermatogenic wave. Gonocyte development involves phases of quiescence, cell proliferation, migration, and differentiation. Spermatogonia, on the other hand, remain located at the basement membrane of the seminiferous tubules throughout their successive phases of proliferation and differentiation. Apoptosis is an integral part of both developmental phases, allowing for the removal of defective cells and the maintenance of proper germ-Sertoli cell ratios. While gonocytes and spermatogonia mitosis are regulated by distinct factors, they both undergo differentiation in response to retinoic acid. In contrast to postpubertal spermatogenesis, the early steps of germ cell development have only recently attracted attention, unveiling genes and pathways regulating SSC self-renewal and proliferation. Yet, less is known on the mechanisms regulating differentiation. The processes leading from gonocytes to spermatogonia have been seldom investigated. While the formation of abnormal gonocytes or SSCs could lead to infertility, defective gonocyte differentiation might be at the origin of testicular germ cell tumors. Thus, it is important to better understand the molecular mechanisms regulating these processes. This review summarizes and compares the present knowledge on the mechanisms regulating mammalian gonocyte and spermatogonial differentiation.

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Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours

Cited by 200 publications

References 34 publications

Male germline stem cells in non-human primates

Male germline stem cells in non-human primates

Combined effects of the two reciprocal t(4;11) fusion proteins MLL·AF4 and AF4·MLL confer resistance to apoptosis, cell cycling capacity and growth transformation

Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges

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