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Author Notes:

Corresponding Author: Email: djkatz@emory.edu

We would like to thank D. Bourc’His for providing the in situ probes; D. Cutler for assistance in mapping the bisulfite clones; and B. Kelly, B. Shur, C. Easley, C. Bean, T. Caspary and members of the Katz lab for helpful discussions on the work and the manuscript.

Thank you to M. Rosenfeld for providing the Lsd1fl/fl mice and D. Castrillon for providing the Vasa-Cre mice.

Subjects:

Research Funding:

D. Myrick was a member of the PREP post-baccalaureate program (5R25GM089615-04).

M. Christopher is supported by the GMB training grant (T32GM008490-21).

P. Donlin-Asp was supported by the BCDB training grant (5T32GM008367).

The work was supported by a grant to D.J.K from the National Science Foundation (IOS1354998).

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

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Journal Title:

PLoS ONE

Volume:

Volume 12, Number 5

Publisher:

, Pages e0177473-e0177473

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2017 Myrick et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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