Telephone: 617-919-2013; Fax: 617-730-0222
Tissue Specific Stem Cells
Article first published online: 24 APR 2013
Copyright © 2013 AlphaMed Press
Volume 31, Issue 5, pages 1001–1009, May 2013
How to Cite
Shinoda, G., De Soysa, T. Y., Seligson, M. T., Yabuuchi, A., Fujiwara, Y., Huang, P. Y., Hagan, J. P., Gregory, R. I., Moss, E. G. and Daley, G. Q. (2013), Lin28a Regulates Germ Cell Pool Size and Fertility. STEM CELLS, 31: 1001–1009. doi: 10.1002/stem.1343
Author contributions: G.S.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; T.Y.S. and M.T.S.: collection and/or assembly of data; A.Y., J.P.H., and R.I.G.: provision of study materials; Y.F. and P.Y.H.: collection and/or assembly of data, and data analysis and interpretation; E.G.M.: provision of study material or patients. G.Q.D.: conception and design, data analysis and interpretation, manuscript writing, and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS February 4, 2013.
- Issue published online: 24 APR 2013
- Article first published online: 24 APR 2013
- Accepted manuscript online: 4 FEB 2013 01:40AM EST
- Manuscript Accepted: 29 DEC 2012
- Manuscript Received: 20 AUG 2012
- Alex's Lemonade Stand Foundation
- Ellison Medical Foundation
- Hematology Center. Grant Number: P30 DK049216-17
- Mouse Embryonic Stem ESCs and Gene Targeting Core
- Eunice Kennedy Shriver NICHD/NIH (SCCPIR. Grant Number: U54-HD28934
- University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core
- Germ cells;
Overexpression of LIN28A is associated with human germ cell tumors and promotes primordial germ cell (PGC) development from embryonic stem cells in vitro and in chimeric mice. Knockdown of Lin28a inhibits PGC development in vitro, but how constitutional Lin28a deficiency affects the mammalian reproductive system in vivo remains unknown. Here, we generated Lin28a knockout (KO) mice and found that Lin28a deficiency compromises the size of the germ cell pool in both males and females by affecting PGC proliferation during embryogenesis. Interestingly however, in Lin28a KO males, the germ cell pool partially recovers during postnatal expansion, while fertility remains impaired in both males and females mated to wild-type mice. Embryonic overexpression of let-7, a microRNA negatively regulated by Lin28a, reduces the germ cell pool, corroborating the role of the Lin28a/let-7 axis in regulating the germ lineage. STEM CELLS 2013;31:1001–1009