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缺失 Dead end1 会导致胚胎睾丸中未能进行性分化的原始生殖细胞发生睾丸畸胎瘤。

Loss of Dead end1 induces testicular teratomas from primordial germ cells that failed to undergo sexual differentiation in embryonic testes.

机构信息

Division of Materials Science and Chemical Engineering, Graduate School of Engineering, Yokohama National University, Yokohama, Kanagawa, Japan.

Research & Development Group, Center for Exploratory Research, Hitachi, Ltd., Kobe, Hyogo, Japan.

出版信息

Sci Rep. 2023 Apr 19;13(1):6398. doi: 10.1038/s41598-023-33706-x.

DOI:10.1038/s41598-023-33706-x
PMID:37076592
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10115811/
Abstract

Spontaneous 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.

摘要

自发性睾丸生殖细胞瘤 (STT) 是一种由多种细胞和组织类型组成的肿瘤，这些细胞和组织类型来源于多能干细胞样细胞，称为胚胎癌细胞 (ECC)。尽管小鼠 ECC 起源于胚胎睾丸中的原始生殖细胞 (PGC)，但 ECC 发育的分子基础仍不清楚。本研究表明，条件性敲除迁移 PGC 中的小鼠 Dead end1 (Dnd1) 可导致 STT 发育。在 Dnd1 条件性敲除 (Dnd1-cKO) 胚胎中，PGC 定植于胚胎睾丸，但未能进行性分化; 随后，一部分 PGC 发育为 ECC。转录组分析表明，PGC 不仅未能进行性分化，而且还容易通过上调睾丸中 Dnd1-cKO 胚胎中原始多能性标记基因的表达而转化为 ECC。因此，我们的结果阐明了 Dnd1 在 STT 形成和 PGC 向 ECC 发育过程中的作用，为 STT 的发病机制提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3234/10115811/b86ab7348357/41598_2023_33706_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3234/10115811/308c97e74c47/41598_2023_33706_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3234/10115811/705eed6ad9b8/41598_2023_33706_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3234/10115811/012e5e7029e3/41598_2023_33706_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3234/10115811/ca2a72925322/41598_2023_33706_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3234/10115811/c1341673d22a/41598_2023_33706_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3234/10115811/6881224cdec1/41598_2023_33706_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3234/10115811/b86ab7348357/41598_2023_33706_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3234/10115811/308c97e74c47/41598_2023_33706_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3234/10115811/705eed6ad9b8/41598_2023_33706_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3234/10115811/012e5e7029e3/41598_2023_33706_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3234/10115811/ca2a72925322/41598_2023_33706_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3234/10115811/c1341673d22a/41598_2023_33706_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3234/10115811/6881224cdec1/41598_2023_33706_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3234/10115811/b86ab7348357/41598_2023_33706_Fig7_HTML.jpg

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本文引用的文献

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