Understanding Forkhead Transcription Factor FOXC2's Role in Regulating Murine Spermatogonial Stem Cells

Date

2022

Authors

Villalon, Stephanie Alejandra

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Abstract

Spermatogonial Stem Cells (SSCs) are a small subpopulation of stem cells that sustain the seminiferous epithelium in the male gonads. These cells give rise to all subsequent spermatogenic cell types and ultimately to differentiated, mature spermatozoa. Following mitosis, daughter cells of SSCs must self-renew to sustain the SSC population or transition to progenitor spermatogonia (progenitors) to contribute to the spermatogenic differentiation pathway. SSC fate and function are regulated by a series of intricate mechanisms, including epigenetic programming and transcription factor networks. Previous studies identified genes that are differentially expressed in SSCs and progenitors and characterized differential epigenetic programming at associated gene promoters and enhancers, and de novo motif discovery identified candidate regulators of this differential programming, including the Forkhead box class "C" 2 transcription factor, FOXC2. Here we examined the expression of the Foxc2 gene at the RNA and protein levels in prospermatogonia and spermatogonia, by mining existing RNA- seq data and conducting immunofluorescence histochemistry (IHC) experiments. In addition, we examined genome-wide binding patterns (cistromes) of FOXC2 by conducting chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) in SSCs and progenitors. Finally, we mined existing epigenomic profiling data to identify coincidental occurrence of FOXC2 binding with other epigenetic parameters at regulatory regions associated with genes differentially expressed in SSCs and progenitors. Previous reports have suggested that FOXC2 and other FOX family members may act as pioneer factors that contribute to initial specification and/or subsequent maintenance of cell fate. Our results are consistent with the notion that FOXC2 is a candidate regulator of initial specification and/or ongoing maintenance of SSC cell fate.

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Keywords

Epigenetics, FOXC2, Spermatogonial Stem Cells, Transcription Factor

Citation

Department

Neuroscience, Developmental and Regenerative Biology