MicroRNA-224 regulates self-renewal of mouse spermatogonial stem cells via targeting DMRT1.
MicroRNAs (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 (SSC) homeostasis remain unclear. In the present study, we report for the first time that miR-224 is highly expressed in mouse SSCs. Functional assays using miRNA mimics and inhibitors reveal that miR-224 is essential for differentiation of SSCs. Mechanistically, miR-224 promotes differentiation of SSCs via targeting doublesex and Mab-3-related transcription factor 1 (DMRT1). Moreover, WNT/β-catenin signalling pathway is involved in miR-224-mediated regulation of SSCs self-renewal. We further demonstrate that miR-224 overexpression increases the expression of GFRα1 and PLZF, accompanied by the down-regulation of DMRT1 in mouse testes. Our findings provide novel insights into molecular mechanisms regulating differentiation of SSCs and may have important implications for regulating male reproduction.
Department of Reproduction, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Na
N
Cui
Department of Reproduction, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Guimin
G
Hao
Department of Reproduction, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Zhiming
Z
Zhao
Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Feng
F
Wang
Department of Reproduction, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Jinfeng
J
Cao
Department of Reproduction, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Aimin
A
Yang
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D000066673:Cell Self Renewal / Q000235:genetics*; D005786:Gene Expression Regulation; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D013093:Spermatogonia / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013737:Testis / Q000166:cytology; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D060449:Wnt Signaling Pathway / Q000235:genetics
D020413:3' Untranslated Regions; D015415:Biomarkers; C110547:DMRT1 protein; C494988:Gfra1 protein, mouse; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D051741:Kruppel-Like Transcription Factors; C584584:MIRN224 microRNA, mouse; D035683:MicroRNAs; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D014157:Transcription Factors; C513267:Zbtb16 protein, mouse
DMRT1; differentiation; miR-224; reproduction; spermatogonial stem cells