title: Expression of Cnnm1 and Its Association with Stemness, Cell Cycle, and Differentiation in Spermatogenic Cells in Mouse Testis.
abstract: Cyclin M1 (CNNM1) functions as a copper storage protein in neuronal cells. We report that Cnnm1 is expressed in mouse testis and brain and has a coding sequence of 1761 bp that encodes a 586 amino acid protein with a molecular weight of 66 kDa. Cnnm1 is expressed in the testes of mice from neonatal to adult stages with relatively higher levels in neonates. CNNM1 expression appeared to be restricted to c-KIT- and OCT3/4-positive cells in the testis, indicating that they are early spermatogonial cells. Spermatogonial stem cells in primary culture expressed Cnnm1, and their differentiation into embryoid body-like clusters in vitro resulted in the loss of Cnnm1 expression. Silencing of Cnnm1 in GC1-spg cells resulted in a significant reduction in the number of cells in G1 phase with concomitant increase in the numbers of cells in both S and G2/M phases. Further, retinoic acid downregulated the expression of Cnnm1 in GC1-spg cells. We conclude that CNNM1 is associated with stemness and self-renewal, and its downregulation triggers differentiation in spermatogonial cells in mouse.
authors.affiliation: Division of Molecular Reproduction, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
authors.forename: Uma
authors.initials: U
authors.lastname: Chandran
authors.affiliation: Division of Molecular Reproduction, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
authors.forename: Sivankutty
authors.initials: S
authors.lastname: Indu
authors.affiliation: Division of Molecular Reproduction, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
authors.forename: Anil T R
authors.initials: AT
authors.lastname: Kumar
authors.affiliation: Division of Molecular Reproduction, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
authors.forename: A N
authors.initials: AN
authors.lastname: Devi
authors.affiliation: Division of Molecular Reproduction, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
authors.forename: Irfan
authors.initials: I
authors.lastname: Khan
authors.affiliation: Division of Molecular Reproduction, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
authors.forename: Diwas
authors.initials: D
authors.lastname: Srivastava
authors.affiliation: Division of Molecular Reproduction, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India kumarp@rgcb.res.in.
authors.forename: Pradeep G
authors.initials: PG
authors.lastname: Kumar
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D013093:Spermatogonia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D027682:Cation Transport Proteins; C523974:Cnnm1 protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D014212:Tretinoin; D019009:Proto-Oncogene Proteins c-kit
keywords: Cnnm1; cell cycle; germline stem cell; retinoic acid; spermatogenesis; testis