Micro<scp>RNA</scp>‐224 regulates self‐renewal of mouse spermatogonial stem cells <i>via</i> targeting <scp>DMRT</scp>1

<jats:title>Abstract</jats:title><jats:p>Micro<jats:styled-content style="fixed-case">RNA</jats:styled-content>s (miRs) play a key role in the control of gene expression in a wide array of tissue systems, where their functions include the regulation of self‐renewal, cellular differentiation, proliferation and apoptosis. However, the function and mechanisms of individual miRs in regulating spermatogonial stem cell (<jats:styled-content style="fixed-case">SSC</jats:styled-content>) homeostasis remain unclear. In the present study, we report for the first time that miR‐224 is highly expressed in mouse <jats:styled-content style="fixed-case">SSC</jats:styled-content>s. Functional assays using mi<jats:styled-content style="fixed-case">RNA</jats:styled-content> mimics and inhibitors reveal that miR‐224 is essential for differentiation of <jats:styled-content style="fixed-case">SSC</jats:styled-content>s. Mechanistically, miR‐224 promotes differentiation of <jats:styled-content style="fixed-case">SSC</jats:styled-content>s <jats:italic>via</jats:italic> targeting doublesex and Mab‐3‐related transcription factor 1 (<jats:styled-content style="fixed-case">DMRT</jats:styled-content>1). Moreover, <jats:styled-content style="fixed-case">WNT</jats:styled-content>/β‐catenin signalling pathway is involved in miR‐224‐mediated regulation of <jats:styled-content style="fixed-case">SSC</jats:styled-content>s self‐renewal. We further demonstrate that miR‐224 overexpression increases the expression of <jats:styled-content style="fixed-case">GFR</jats:styled-content>α1 and <jats:styled-content style="fixed-case">PLZF</jats:styled-content>, accompanied by the down‐regulation of <jats:styled-content style="fixed-case">DMRT</jats:styled-content>1 in mouse testes. Our findings provide novel insights into molecular mechanisms regulating differentiation of <jats:styled-content style="fixed-case">SSC</jats:styled-content>s and may have important implications for regulating male reproduction.</jats:p>