Inhibitor of DNA binding 4 is expressed selectively by single spermatogonia in the male germline and regulates the self-renewal of spermatogonial stem cells in mice

Melissa J Oatley; Amy V Kaucher; Karen E Racicot; Jon M Oatley

doi:10.1095/biolreprod.111.091330

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Inhibitor of DNA binding 4 is expressed selectively by single spermatogonia in the male germline and regulates the self-renewal of spermatogonial stem cells in mice

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Inhibitor of DNA binding 4 is expressed selectively by single spermatogonia in the male germline and regulates the self-renewal of spermatogonial stem cells in mice

Melissa J Oatley, Amy V Kaucher, Karen E Racicot and Jon M Oatley

Biology of reproduction, Vol.85(2), pp.347-356

08/2011

DOI: https://doi.org/10.1095/biolreprod.111.091330

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https://hdl.handle.net/2376/115632

PMID: 21543770

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Abstract

Testis - metabolism

Gene Silencing

Gene Expression Regulation - physiology

Inhibitor of Differentiation Proteins - genetics

Male

Inhibitor of Differentiation Proteins - metabolism

Stem Cells - cytology

Stem Cells - metabolism

Spermatogonia - metabolism

Animals

Biomarkers

Mice

RNA, Small Interfering

Continual spermatogenesis at a quantitatively normal level is required to sustain male fertility. The foundation of this process relies on maintenance of an undifferentiated spermatogonial population consisting of spermatogonial stem cells (SSCs) that self-renew as well as transient amplifying progenitors produced by differentiation. In mammals, type A(single) spermatogonia form the SSC population, but molecular markers distinguishing these from differentiating progenitors are undefined and knowledge of mechanisms regulating their functions is limited. We show that in the mouse male germline the transcriptional repressor ID4 is expressed by a subpopulation of undifferentiated spermatogonia and selectively marks A(single) spermatogonia. In addition, we found that ID4 expression is up-regulated in isolated SSC-enriched fractions by stimulation from GDNF, a key growth factor driving self-renewal. In mice lacking ID4 expression, quantitatively normal spermatogenesis was found to be impaired due to progressive loss of the undifferentiated spermatogonial population during adulthood. Moreover, reduction of ID4 expression by small interfering RNA treatment abolished the ability of wild-type SSCs to expand in vitro during long-term culture without affecting their survival. Collectively, these results indicate that ID4 is a distinguishing marker of SSCs in the mammalian germline and plays an important role in the regulation of self-renewal.

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Title: Inhibitor of DNA binding 4 is expressed selectively by single spermatogonia in the male germline and regulates the self-renewal of spermatogonial stem cells in mice
Creators: Melissa J Oatley - Center for Reproductive Biology and Health, Department of Dairy and Animal Science, College of Agricultural Sciences, The Pennsylvania State University, University Park, PA, USA
Amy V Kaucher
Karen E Racicot
Jon M Oatley
Publication Details: Biology of reproduction, Vol.85(2), pp.347-356
Academic Unit: Molecular Biosciences, School of
Publisher: United States
Grant note: R01 HD061665-02 / NICHD NIH HHS R01 HD061665-01 / NICHD NIH HHS R21 HD058137 / NICHD NIH HHS HD061665 / NICHD NIH HHS HD058137 / NICHD NIH HHS R01 HD061665 / NICHD NIH HHS
Identifiers: 99900547687901842
Language: English
Resource Type: Journal article