A novel embryonic stem cell line derived from the common marmoset monkey (Callithrix jacchus) exhibiting germ cell-like characteristics

Müller, Thomas; Fleischmann, Gesine; Eildermann, Katja; Mätz‐Rensing, Kerstin; Horn, Peter A.; Sasaki, Erika; Behr, Rüdiger

doi:10.1093/humrep/dep012

Cited by 65 publications

(76 citation statements)

References 42 publications

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“…Each marmoset ES cell line also showed a unique gene expression profile: clone No. 40 expressed NR6A1 (GCNF) but not BOLL (BOULE), whereas clone cjes001 exhibited the opposite expression in the previous report (Muller et al 2009). It remains to be elucidated whether there is any further correlation between marker gene expression and the differentiation potency of ES cells.…”

Section: Molecular Signature Of Marmoset Spermatogenesismentioning

confidence: 65%

“…To date, others and we have established several lines of marmoset ES cells (Sasaki et al 2005, Muller et al 2009) and induced pluripotent stem cells from fetal liver cells and neonatal skin fibroblasts (Tomioka et al 2010, Wu et al 2010. Both types of pluripotent stem cells were able to differentiate in vitro, suggesting the potential for in vitro germ cell production.…”

Section: Molecular Signature Of Marmoset Spermatogenesismentioning

confidence: 99%

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Molecular signatures to define spermatogenic cells in common marmoset (Callithrix jacchus)

Lin

Imamura²,

Sano³

et al. 2012

Reproduction

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Germ cell development is a fundamental process required to produce offspring. The developmental program of spermatogenesis has been assumed to be similar among mammals. However, recent studies have revealed differences in the molecular properties of primate germ cells compared with the well-characterized mouse germ cells. This may prevent simple application of rodent insights into higher primates. Therefore, thorough investigation of primate germ cells is necessary, as this may lead to the development of more appropriate animal models. The aim of this study is to define molecular signatures of spermatogenic cells in the common marmoset, Callithrix jacchus. Interestingly, NANOG, PRDM1, DPPA3 (STELLA), IFITM3, and ZP1 transcripts, but no POU5F1 (OCT4), were detected in adult marmoset testis. Conversely, mouse testis expressed Pou5f1 but not Nanog, Prdm1, Dppa3, Ifitm3, and Zp1. Other previously described mouse germ cell markers were conserved in marmoset and mouse testes. Intriguingly, marmoset spermatogenic cells underwent dynamic protein expression in a developmental stage-specific manner; DDX4 (VASA) protein was present in gonocytes, diminished in spermatogonial cells, and reexpressed in spermatocytes. To investigate epigenetic differences between adult marmoset and mice, DNA methylation analyses identified unique epigenetic profiles to marmoset and mice. Marmoset NANOG and POU5F1 promoters in spermatogenic cells exhibited a methylation status opposite to that in mice, while the DDX4 and LEFTY1 loci, as well as imprinted genes, displayed an evolutionarily conserved methylation pattern. Marmosets have great advantages as models for human reproductive biology and are also valuable as experimental nonhuman primates; thus, the current study provides an important platform for primate reproductive biology, including possible applications to humans.

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Section: Molecular Signature Of Marmoset Spermatogenesismentioning

confidence: 65%

Section: Molecular Signature Of Marmoset Spermatogenesismentioning

confidence: 99%

Molecular signatures to define spermatogenic cells in common marmoset (Callithrix jacchus)

Lin

Imamura²,

Sano³

et al. 2012

Reproduction

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“…c-CBL plays an important role in myeloid cells since mutations in this gene result in myeloid malignancies (Murati et al, 2012;Katzav and Schmitz, 2015;Lv et al, 2017). The role of c-CBL in human spermatogonia has not been investigated in detail so far since, to our knowledge, the fertility status and testicular histology of the patients carrying c-CBL mutations has not been analyzed.…”

Section: Discussionmentioning

confidence: 99%

“…c-CBL also plays an important clinical role. Myeloid malignancies originate from hematopoietic stem or progenitor cells of the myeloid lineage and mutations in the c-CBL gene have been found in many patients with this type of blood cell malignancies (Murati et al, 2012;Katzav and Schmitz, 2015;Lv et al, 2017). Using a combined microarray and immunohistochemistry approach, von Kopylow and colleagues (von Kopylow et al, 2010) further demonstrated that c-CBL is expressed in the human testis specifically by spermatogonia.…”

Section: Introductionmentioning

confidence: 99%

The ubiquitin ligase c-CBL is expressed in undifferentiated marmoset monkey pluripotent stem cells but is not a general stem cell marker

et al. 2017

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Abstract. The protein c-CBL is a ubiquitin ligase. It catalyzes the last step of the transfer of ubiquitin to target proteins. Upon completion of polyubiquitination, the target proteins are degraded. Clinically, it is important that c-CBL is mutated in a subset of patients who develop myeloid malignancies, which are diseases of the hematopoietic stem or progenitor cells. c-CBL has also been shown to be expressed by human spermatogonia. The whole spermatogonial cell population possesses a subset that comprises also the spermatogonial stem cells. Based on these findings we hypothesized that c-CBL might be a general stem cell marker. To test this, we first validated the antibody using marmoset bone marrow and adult testis. In both tissues, the expected staining pattern was observed. Western blot analysis revealed only one band of the expected size. Then, we examined the expression of c-CBL in marmoset monkey embryonic stem (ES) cells, induced pluripotent stem (iPS) cells and adult stem cells. We found that c-CBL is strongly expressed in undifferentiated marmoset iPS cells and ES cells. However, adult stem cells in the gut and the stomach did not express c-CBL, indicating that c-CBL is not a general stem cell marker. In summary, c-CBL is strongly expressed in pluripotent stem cells of the marmoset monkey as well as in selected adult stem cell types. Future studies will define the function of c-CBL in pluripotent stem cells.

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“…Marmosets were the first transgenic primates to demonstrate germline transmission 12 and their amenability to stem cell technologies is notable among primates. [13][14][15] They have also been suggested as particularly suitable models for gene therapy studies. 16,17 Part of the reason for this may be their limited MHC diversity, unique among primates.…”

mentioning

confidence: 99%

Naturally occurring, physiologically normal, primate chimeras

2012

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A novel embryonic stem cell line derived from the common marmoset monkey (Callithrix jacchus) exhibiting germ cell-like characteristics

Abstract: The cjes001 cells represent a new pluripotent ESC line with evidence for enhanced spontaneous differentiation potential into germ cells. This cjes001 line will be very valuable for comparative studies on primate ESC biology.

Cited by 65 publications

References 42 publications

Molecular signatures to define spermatogenic cells in common marmoset (Callithrix jacchus)

Molecular signatures to define spermatogenic cells in common marmoset (Callithrix jacchus)

The ubiquitin ligase c-CBL is expressed in undifferentiated marmoset monkey pluripotent stem cells but is not a general stem cell marker

Naturally occurring, physiologically normal, primate chimeras

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