Spermatogenesis is the process where sperm are made, and it involves thousands of genes and proteins that are activated and repressed. The function of a large proportion of these genes and proteins remains unknown and testis harbors many "missing proteins" (MPs).

One of the most complex organs in the human body is the testis, where spermatogenesis takes place. This physiological process involves thousands of genes and proteins that are activated and repressed, making testis the organ with the highest number of tissue-specific genes. However, the function of a large proportion of the corresponding proteins remains unknown and testis harbors many missing proteins, defined as products of protein-coding genes that lack experimental mass spectrometry evidence.

In an international study led by HPA researchers and collaborators, an integrated omics approach was used for exploring the cell type-specific protein localization of genes with an elevated expression in testis. By combining genome-wide transcriptomics analysis with immunohistochemistry, more than 500 proteins with distinct testicular protein expression patterns were identified, and these were selected for in-depth characterization of their in situ expression in eight different testicular cell types. The cell type-specific protein expression patterns allowed the researchers to identify six distinct clusters of expression at different stages of spermatogenesis. The analysis highlighted numerous poorly characterized proteins in each of these clusters, whose expression overlapped with that of known proteins involved in spermatogenesis, including 85 proteins with an unknown function and 60 proteins classified as MPs. Furthermore, the in situ distribution of several proteins that previously lacked spatial information and cell type-specific expression within the testis were identified in the study. The testis elevated expression levels both at the RNA and protein levels suggest that these proteins are related to testis-specific functions.

In summary, the study demonstrated the power of combining genome-wide transcriptomics analysis with antibody-based protein profiling to explore the cell type-specific expression of both well-known proteins and MPs. The analyzed proteins constitute important targets for further testis-specific research in male reproductive disorders.

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Access the full text article here: Pineau C et al. Cell type-specific expression of testis elevated genes based on transcriptomics and antibody-based proteomics. J Proteome Res. 2019.

Feria Hikmet Noraddin