title: BMP4/Smad signaling pathway induces the differentiation of mouse spermatogonial stem cells via upregulation of Sohlh2.
abstract: Spermatogonial stem cells (SSCs) capable of self-renewal and differentiation are the foundation for spermatogenesis. Although several factors that govern these processes have been investigated, the underlying molecular mechanisms have not been fully elucidated. Here, we investigated the role of BMP4 in mouse SSC differentiation, and found that SSCs cultured in the presence of BMP4 underwent differentiation, characterized by downregulation of SSC self-renewal markers, Plzf, and upregulation of SSC differentiation marker, c-kit. Smad1/5/8 proteins were phosphorylated during BMP4-induced differentiation. The effects of BMP4 on SSCs were blocked by BMP4 inhibitor (Dorsomorphin). The activation of BMP4/Smad signaling pathway in SSCs increased the expression of Sohlh2, which is involved in the early differentiation of spermatogonia. Knockdown sohlh2 expression by RNA interference abolished the effect of BMP4 on SSC differentiation and the upregulation of c-kit expression. Overall, our results suggest that BMP4 plays an important role during the early differentiation of SSCs via upregulation of sohlh2.
authors.affiliation: Department of Histology and Embryology, School of Medicine, Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan, 250012, People's Republic of China; Obstetric Genetic Disease Laboratory, Maternal and Child Health Hospital of Zibo City, Zibo, 255029, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Yuecun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.forename: Jinhao
authors.initials: J
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Hao
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D008297:Male; D051379:Mice; D010766:Phosphorylation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology; D013093:Spermatogonia / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D055415:Bone Morphogenetic Protein 4; D019009:Proto-Oncogene Proteins c-kit; D012333:RNA, Messenger; D051785:Smad Proteins; C525810:Bmp4 protein, mouse; C515516:Sohlh2 protein, mouse
keywords: BMP4; Smad1/5/8; Sohlh2; differentiation; spermatogonial stem cells