對30個候選基因所做的一個RNA干涉篩選，識別出Lin28（let-7 microRNA處理的一個負調(diào)控因子）為原始生殖細胞發(fā)育（這是發(fā)育中的胚胎內(nèi)所發(fā)生的一個過程,，它選擇注定要產(chǎn)生精子和卵子的細胞）的一個潛在關(guān)鍵調(diào)控因子,。另外，Lin28水平在原發(fā)性人類生殖細胞腫瘤中升高,，說明它也許也與生殖細胞惡性腫瘤有關(guān),。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 460, 909-913 (13 August 2009) | doi:10.1038/nature08210
A role for Lin28 in primordial germ-cell development and germ-cell malignancy
Jason A. West1,2, Srinivas R. Viswanathan1,2, Akiko Yabuuchi1,2, Kerianne Cunniff1,2, Ayumu Takeuchi1,2, In-Hyun Park1,2, Julia E. Sero3, Hao Zhu1,2, Antonio Perez-Atayde3, A. Lindsay Frazier1,4, M. Azim Surani5 & George Q. Daley1,2,6,7
1 Division of Pediatric Hematology/Oncology, Children's Hospital Boston and the Dana-Farber Cancer Institute,
2 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA
3 Department of Pathology, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts 02115, USA
4 Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
5 Wellcome Trust Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
6 Manton Center for Orphan Disease Research, Boston, Massachusetts 02115, USA
7 Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA
The rarity and inaccessibility of the earliest primordial germ cells (PGCs) in the mouse embryo thwart efforts to investigate molecular mechanisms of germ-cell specification. stella (also called Dppa3) marks the rare founder population of the germ lineage1, 2. Here we differentiate mouse embryonic stem cells carrying a stella transgenic reporter into putative PGCs in vitro. The Stella+ cells possess a transcriptional profile similar to embryo-derived PGCs, and like their counterparts in vivo, lose imprints in a time-dependent manner. Using inhibitory RNAs to screen candidate genes for effects on the development of Stella+ cells in vitro, we discovered that Lin28, a negative regulator of let-7 microRNA processing3, 4, 5, 6, is essential for proper PGC development. Furthermore, we show that Blimp1 (also called Prdm1), a let-7 target and a master regulator of PGC specification7, 8, 9, can rescue the effect of Lin28 deficiency during PGC development, thereby establishing a mechanism of action for Lin28 during PGC specification. Overexpression of Lin28 promotes formation of Stella+ cells in vitro and PGCs in chimaeric embryos, and is associated with human germ-cell tumours. The differentiation of putative PGCs from embryonic stem cells in vitro recapitulates the early stages of gamete development in vivo, and provides an accessible system for discovering novel genes involved in germ-cell development and malignancy.
