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

PloS One
Dexter A MyrickDavid J Katz

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.

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Citations

Jul 12, 2017·Genetics·Juan D RodriguezDavid J Katz
Apr 6, 2019·Biology of Reproduction·Romain LambrotSarah Kimmins
Nov 9, 2019·Nucleic Acids Research·Igor MačinkovićAlexander Brehm
Oct 8, 2019·Molecular Reproduction and Development·Aastha PandeyGopal Gupta
May 28, 2020·International Journal of Molecular Sciences·Maria E TevesPaulene Sapao
Oct 19, 2017·Epigenetics & Chromatin·Michael A ChristopherDavid J Katz
Nov 24, 2019·Cancers·Panagiotis KarakaidosAngeliki Magklara
Apr 23, 2020·Frontiers in Cell and Developmental Biology·Betina GonzálezCandela R González
Apr 5, 2020·Animals : an Open Access Journal From MDPI·Zhenhua ShenYucai Zheng
Jun 24, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Sarder ArifuzzamanRabeya Khatun

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Datasets Mentioned

BETA
GTX7334

Methods Mentioned

BETA
transgenic
immunoprecipitation
ChIP
biopsies
genotyping
PCR

Software Mentioned

BiQ Analyzer

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