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Transcriptional Analysis of Histone Deacetylase Family Members Reveal Similarities Between Differentiating and Aging Spermatogonial Stem Cells

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Abstract

The differentiation of adult stem cells involves extensive chromatin remodeling, mediated in part by the gene products of histone deacetylase (HDAC) family members. While the transcriptional downregulation of HDACs can impede stem cell self-renewal in certain contexts, it may also promote stem cell maintenance under other circumstances. In self-renewing, differentiating, and aging spermatogonial stem cells (SSCs), the gene expression dynamics of HDACs have not yet been characterized. To gain further insight with these studies, we analyzed the transcriptional profiles of six HDAC family members, previously identified to be the most highly expressed in self-renewing SSCs, during stem cell differentiation and aging. Here we discovered that in both differentiating and aging SSCs the expression of Sirt4 increases, while the expression of Hdac2, Hdac6, and Sirt1 decreases. When SSCs are exposed to the lifespan-enhancing drug rapamycin in vivo, the resultant HDAC gene expression patterns are opposite of those seen in the differentiating and aging SSCs, with increased Hdac2, Hdac6, and Sirt1 and decreased Hdac8, Hdac9, and Sirt4. Our findings suggest that HDACs important for stem cell maintenance and oxidative capacity are downregulated as adult stem cells differentiate or age. These results provide important insights into the epigenetic regulation of stem cell differentiation and aging in mammals.

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Acknowledgments

We thank Shannon Gallagher, Rachel Anderson, and Kristin Kalita for their assistance with these experiments, and the Medical Research Institute Council at Children’s Memorial Research Center for their generous financial support. C.J.P. is the recipient of an NIH Pathway-to-Independence Award from the Eunice Kennedy Shriver National Institute of Child Health & Human Development. This work was supported by an NIH grant to C.J.P. (5R00 HD055330-5).

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The authors declare no potential conflicts of interest.

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Authors and Affiliations

  1. Human Molecular Genetics Program, Children’s Memorial Research Center, Chicago, IL, 60614, USA

    Amber E. Kofman, Jessica M. Huszar & Christopher J. Payne

  2. Driskill Graduate Program, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA

    Amber E. Kofman, Jessica M. Huszar & Christopher J. Payne

  3. Departments of Pediatrics and Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA

    Christopher J. Payne

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  1. Amber E. Kofman
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Correspondence to Christopher J. Payne.

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Kofman, A.E., Huszar, J.M. & Payne, C.J. Transcriptional Analysis of Histone Deacetylase Family Members Reveal Similarities Between Differentiating and Aging Spermatogonial Stem Cells. Stem Cell Rev and Rep 9, 59–64 (2013). https://doi.org/10.1007/s12015-012-9392-5

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