Unknown,Transcriptomics,Genomics,Proteomics

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Role of retinoblastoma protein (Rb) in mouse Sertoli cells function

ABSTRACT: Gene expression profiling study of Sertoli cells (Sc)-specific Retinoblastoma (Rb) knockout (KO) mice. We generated a Sc-specific Rb knockout (Sc-RbKO) line and characterised its testicular phenotype. Sc-RbKO showed a progressive germ cell depletion leading to infertility and Sc dysfunction. We observed that up to 10 days old, Sc-RbKO mice present a phenotype similar to that of their WT siblings. This age was choosen to study the gene expression changes that would eventually lead to the described phenotypical changes. Sc-RbKO testis gene expression was compared to WT and to Sc-Rb+/- samples. Our Microarray results show changes of many genes involved in cell cycle control, DNA repair, apoptosis and misregulation of genes that may be important for proper Sertoli cell function such as tight junction formation, cell membrane and tissue remodeling. Total RNA extracted from 12 testicular samples, 5 controls, 3 hetorozygotes and 4 homozygotes.

ORGANISM(S): Mus musculus

SUBMITTER: Sonia Bourguiba-Hachemi

PROVIDER: E-GEOD-22234 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Immune privileged Sertoli cells (SC) survive when transplanted across immunological barriers and prolong the survival of co-transplanted allogeneic and xenogeneic cells in rodent models. However, the mechanism for this survival and protection remains unresolved. We have recently identified a mouse Sertoli cell line (MSC-1) that lacks some of the immunoprotective abilities associated with primary SC. The objective of this study was to compare the survival and gene expression profiles of primary SC and MSC-1 cells to identify factors or immune-related pathways potentially important for SC immune privilege. Primary SC or MSC-1 cells were transplanted as allografts to the renal subcapsular area of naïve BALB/c mice and cell survival was analyzed by immunohistochemistry. Additionally, transcriptome differences were investigated by microarray and pathway analyses. While primary SC were detected within the grafts with 100% graft survival throughout the 20-day study, MSC-1 cells w ere rejected between 11 and 14 days with 0% graft survival at 20 days post-transplantation. Microarray analysis identified 3198 genes that were differentially expressed with a ± 4-fold or higher level in primary SC. Cluster and pathway analyses indicate that the mechanism of SC immune privilege is likely complex with multiple immune modulators being involved such as immunosuppressive cytokines and complement inhibitors, lipid mediators for controlling inflammation, and junctional molecules that control leukocyte movement in and out of the immune privileged space. Further study of these immune modulators will increase our understanding of SC immune privilege and in the long-term lead to improvements in transplantation success. We conducted microarray and pathway analyses to identify genes and immune-related pathways differentially regulated by aggregated primary Sertoli cells and MSC-1 cell line. Aggregated 19 to 20-day mice primary Sertoli cells and MSC-1 cell line were used to determine the global transcriptome differences important for the survival and protection of transplanted cells.

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Role of retinoblastoma protein (Rb) in mouse Sertoli cells function

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