Expression ofCnnm1and Its Association with Stemness, Cell Cycle, and Differentiation in Spermatogenic Cells in Mouse Testis1

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Abstract

Cyclin M1 (CNNM1) functions as a copper storage protein in neuronal cells. We report thatCnnm1is 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.Cnnm1is 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 expressedCnnm1, and their differentiation into embryoid body-like clusters in vitro resulted in the loss ofCnnm1expression. Silencing ofCnnm1in 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 ofCnnm1in GC1-spg cells. We conclude that CNNM1 is associated with stemness and self-renewal, and its downregulation triggers differentiation in spermatogonial cells in mouse.

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