title: PLZF-Induced Upregulation of CXCR4 Promotes Dairy Goat Male Germline Stem Cell Proliferation by Targeting Mir146a.
abstract: Previous studies have shown that promyelocytic leukemia zinc finger (PLZF), chemokine (C-X-C motif) receptor 4 (CXCR4) and mir146a were associated with the self-renewal of mouse spermatogonial stem cells (SSCs); however, there is little information on their effects on the fate of livestock SSCs. Here, we have identified a regulatory pathway in dairy goat mGSCs, involving PLZF, mir146a and the SDF-1 receptor CXCR4. PLZF overexpression downregulated mir146a and simultaneously upregulated the expression of CXCR4 protein, whereas PLZF knockdown (siPLZF) induced the specifically opposite effects. The in vitro assays demonstrated that PLZF specifically interacts with and suppresses the mir146a promoter, and mir146a targets CXCR4 to impede its translation. The levels of ERK1/2 phosphorylation in the mGSCs overexpressed CXCR4 and PLZF were upregulated, respectively, whereas mir146a expression was decreased and CXCR4 protein was increased. Mir146a overexpression and siPLZF impaired mGSC proliferation and differentiation, however, Mir146a knockdown induced the opposite effects. The effects of PLZF and mir146a were mediated regulation by mir146a and CXCR4, respectively. Overexpression of CXCR4 or addition of CXCL12 in cultures of dairy goat mGSCs resulted in the upregulation of their signaling, and the phosphorylation of ERK1/2 was increased. Collectively, these findings indicate that PLZF is an important transcription factor in the regulation of the expression of CXCR4 to promote dairy goat mGSC proliferation by targeting mir146a.
authors.affiliation: College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Shaanxi, 712100, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Mu
authors.affiliation: College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Shaanxi, 712100, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Shaanxi, 712100, China.|College of Agriculture, Guangdong Ocean University, Zhanjiang, Guangdong, 524088, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Wu
authors.affiliation: College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Shaanxi, 712100, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Zheng
authors.affiliation: College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Shaanxi, 712100, China.
authors.forename: Yuanxin
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Shaanxi, 712100, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Shaanxi, 712100, China.
authors.forename: Wencong
authors.initials: W
authors.lastname: Song
authors.affiliation: College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Shaanxi, 712100, China.
authors.forename: Jinglu
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Shaanxi, 712100, China.|College of Life Science, Yulin University, Yulin, Shaanxi, 719000, China.
authors.forename: Haijing
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Key Laboratory for Mammalian Reproductive Biology and Biotechnology, Ministry of Education, Inner Mongolia University, Hohhot, 010021, China.
authors.forename: Guangpeng
authors.initials: G
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Shaanxi, 712100, China.
authors.forename: Jinlian
authors.initials: J
authors.lastname: Hua
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D003612:Dairying; D005260:Female; D005786:Gene Expression Regulation; D006041:Goats; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013093:Spermatogonia / Q000166:cytology / Q000378:metabolism*
chemical_list: D054377:Chemokine CXCL12; D051741:Kruppel-Like Transcription Factors; D035683:MicroRNAs; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: CXCL12-CXCR4; DAIRY GOAT; MALE GERMLINE STEM CELLS (mGSCs); SELF-RENEWAL; SPERMATOGONIAL STEM CELL (SSC); mir146a