Global human tissue profiling and protein network analysis reveals distinct levels of transcriptional germline-specificity and identifies target genes for male infertility
| Autor: | Romain Mathieu, Aurélie Lardenois, Bertrand Evrard, Wolfgang Schulze, Alexandre Gattiker, Philippe Demougin, Bernard Jégou, Frédéric Chalmel, Michael Primig, Caroline Feig, Christiane Kirchhoff |
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| Přispěvatelé: | Transcriptional networks in gametogenesis and cancer, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Department of Andrology, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Biozentrum [Basel, Suisse], University of Basel (Unibas), School of Life Sciences [Lausanne], Ecole Polytechnique Fédérale de Lausanne (EPFL), Environnement viral et chimique & reproduction, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Target Proteome Somatic cell Amino Acid Motifs interactome Network Gene Germline Male infertility Transcriptome MESH: Amino Acid Motifs 0302 clinical medicine regulatory motifs MESH: Child Cryptorchidism Testis MESH: Animals Child Promoter Regions Genetic MESH: Organ Specificity Oligonucleotide Array Sequence Analysis Genetics Regulation of gene expression 0303 health sciences 030219 obstetrics & reproductive medicine MESH: Testis Rehabilitation Obstetrics and Gynecology Phenotype MESH: Gene Expression Regulation DNA-Binding Proteins MESH: Proteome Organ Specificity Mammalia Specificity MESH: Spermatogenesis Human Adult MESH: Rats Biology MESH: Infertility Male 03 medical and health sciences MESH: Gene Expression Profiling Species Specificity MESH: Cryptorchidism Male sterility MESH: Promoter Regions Genetic medicine Animals Humans MESH: Species Specificity RNA Messenger Spermatogenesis Infertility Male 030304 developmental biology MESH: RNA Messenger Vertebrata Tissue MESH: Humans Male genital diseases Gene Expression Profiling Protein MESH: Adult [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology medicine.disease MESH: Male Rats Gene expression profiling Reproductive Medicine Gene Expression Regulation MESH: Oligonucleotide Array Sequence Analysis transcriptome MESH: DNA-Binding Proteins |
| Zdroj: | Human Reproduction Human Reproduction, 2012, 27 (11), pp.3233-48. ⟨10.1093/humrep/des301⟩ Human Reproduction, Oxford University Press (OUP), 2012, 27 (11), pp.3233-48. ⟨10.1093/humrep/des301⟩ |
| ISSN: | 0268-1161 1460-2350 |
| DOI: | 10.1093/humrep/des301⟩ |
| Popis: | International audience; BACKGROUND: Mammalian spermatogenesis is a process that involves a complex expression program in both somatic and germ cells present in the male gonad. A number of studies have attempted to define the transcriptome of male meiosis and gametogenesis in rodents and primates. Few human transcripts, however, have been associated with testicular somatic cells and germ cells at different post-natal developmental stages and little is known about their level of germline-specificity compared with non-testicular tissues. METHODS: We quantified human transcripts using GeneChips and a total of 47 biopsies from prepubertal children diagnosed with undescended testis, infertile adult patients whose spermatogenesis is arrested at consecutive stages and fertile control individuals. These results were integrated with data from enriched normal germ cells, non-testicular expression data, phenotype information, predicted regulatory DNA-binding motifs and interactome data. RESULTS: Among 3580 genes for which we found differential transcript concentrations in somatic and germ cells present in human testis, 933 were undetectable in 45 embryonic and adult non-testicular tissues, including many that were corroborated at protein level by published gene annotation data and histological high-throughput protein immunodetection assays. Using motif enrichment analyses, we identified regulatory promoter elements likely involved in germline development. Finally, we constructed a regulatory disease network for human fertility by integrating expression signals, interactome information, phenotypes and functional annotation data. CONCLUSIONS: Our results provide broad insight into the post-natal human testicular transcriptome at the level of cell populations and in a global somatic tissular context. Furthermore, they yield clues for genetic causes of male infertility and will facilitate the identification of novel cancer/testis genes as targets for cancer immunotherapies. |
| Databáze: | OpenAIRE |
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