KDM1A/LSD1 regulates the differentiation and maintenance of spermatogonia in mice.

• Type of Material: Article
• Authors: Dexter A. Myrick, Emory University; Michael A. Christopher, Emory University; Alyssa M. Scott, Emory University; Ashley K Simon, Emory University; Paul G. Donlin-Asp, Emory University; William Kelly, Emory University; David Katz, Emory University
• Language: English
• Date: 2017
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2017 Myrick et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0177473
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 12
• Issue: 5
• Start Page: e0177473
• End Page: e0177473
• Grant/Funding Information: D. Myrick was a member of the PREP post-baccalaureate program (5R25GM089615-04).; M. Christopher is supported by the GMB training grant (T32GM008490-21).; The work was supported by a grant to D.J.K from the National Science Foundation (IOS1354998).; P. Donlin-Asp was supported by the BCDB training grant (5T32GM008367).
• Research Categories: Biology, Genetics; Health Sciences, Medicine and Surgery

Abstract

The proper regulation of spermatogenesis is crucial to ensure the continued production of sperm and fertility. Here, we investigated the function of the H3K4me2 demethylase KDM1A/LSD1 during spermatogenesis in developing and adult mice. Conditional deletion of Kdm1a in the testis just prior to birth leads to fewer spermatogonia and germ cell loss before 3 weeks of age. These results demonstrate that KDM1A is required for spermatogonial differentiation, as well as germ cell survival, in the developing testis. In addition, inducible deletion of Kdm1a in the adult testis results in the abnormal accumulation of meiotic spermatocytes, as well as apoptosis and progressive germ cell loss. These results demonstrate that KDM1A is also required during adult spermatogenesis. Furthermore, without KDM1A, the stem cell factor OCT4 is ectopically maintained in differentiating germ cells. This requirement for KDM1A is similar to what has been observed in other stem cell populations, suggesting a common function. Taken together, we propose that KDM1A is a key regulator of spermatogenesis and germ cell maintenance in the mouse.