Author:
Imai Atsuki,Matsuda Kazuya,Niimi Yuki,Suzuki Atsushi
Abstract
AbstractSpontaneous testicular teratomas (STTs) are tumours comprising a diverse array of cell and tissue types, which are derived from pluripotent stem-like cells called embryonal carcinoma cells (ECCs). Although mouse ECCs originate from primordial germ cells (PGCs) in embryonic testes, the molecular basis underlying ECC development remains unclear. This study shows that the conditional deletion of mouse Dead end1 (Dnd1) from migrating PGCs leads to STT development. In Dnd1-conditional knockout (Dnd1-cKO) embryos, PGCs colonise the embryonic testes but fail to undergo sexual differentiation; subsequently, ECCs develop from a portion of the PGCs. Transcriptomic analyses reveal that PGCs not only fail to undergo sexual differentiation but are also prone to transformation into ECCs by upregulating the expression of marker genes for primed pluripotency in the testes of Dnd1-cKO embryos. Thus, our results clarify the role of Dnd1 in developing STTs and developmental process of ECC from PGC, providing novel insights into pathogenic mechanisms of STTs.
Funder
Naito Foundation
Japan Society for the Promotion of Science
Publisher
Springer Science and Business Media LLC
Reference47 articles.
1. Stevens, L. C. & Little, C. C. Spontaneous testicular teratomas in an inbred strain of mice. Proc. Natl. Acad. Sci. USA 40, 1080–1087 (1954).
2. Stevens, L. C. & Hummel, K. P. A description of spontaneous congenital testicular teratomas in strain 129 mice. J. Natl. Cancer Inst. 18, 719–747 (1957).
3. Stevens, L. C. A new inbred subline of mice (129-terSv) with a high incidence of spontaneous congenital testicular teratomas. J. Natl. Cancer Inst. 50, 235–242 (1973).
4. Noguchi, M. et al. The ter mutation responsible for germ cell deficiency but not testicular nor ovarian teratocarcinogenesis in ter/ter congenic mice. Dev. Growth Differ. 38, 59–69 (1996).
5. Youngren, K. K. et al. The ter mutation in the dead end gene causes germ cell loss and testicular germ cell tumours. Nature 435, 360–364 (2005).
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献