Emmie Pohjanen (Stockholm / SE; Stanford, CA / US), Jan N. Hansen (Stockholm / SE; Stanford, CA / US), Jannika Patz (Muenster / DE), Christoph Brenker (Muenster / DE), Alexandra Johannesson (Stockholm / SE), Jenny Fall (Stockholm / SE), Mathias Uhlen (Stockholm / SE), Timo Strünker (Muenster / DE), Ulrika Axelsson (Stockholm / SE), Emma Lundberg (Stockholm / SE; San Francisco, CA / US; Stanford, CA / US)
Sperm are among the most specialized cell types in the human body. Not only do they lack most of the organelles that are present in other cell types, but they also have a flagellum. Sperm cells have a massive task of navigating and traveling through the female reproductive tract towards the ovum and utilize the flagellum, which is a specialized motile cilium, as their motor, rudder, and sensor. For instance, sensory proteins on the flagellar membrane, such as ion channels, detect environmental signals and initiate a downstream signaling cascade that orchestrates the flagellar beat. Little is known about the signaling pathways and mechanisms that drive the flagellar beat, including the spatial information of signaling components in the flagella. Additionally, only a few of the hundred million of sperm cells ejaculated, reach the ovum. This indicates that there might be a certain heterogeneity in sperm cells that only allow some of them to complete the journey.
In this study, we perform a comprehensive mapping of the subcellular spatial distribution of the protein repertoire in the human sperm cell, on the single-cell level. By utilizing antibody-based spatial proteomics with validated antibodies from the Human Protein Atlas (HPA) library, we are able to distinguish 12 subcellular structures of the sperm cell. We observe that roughly 60% of the sperm proteome shows heterogeneity on the single-cell level. By comparing the variable proteome to infertility databases, we will gain better insight to the factors contributing to male infertility cases.
We believe that mapping the human sperm flagellum proteome will greatly contribute to our understanding of sperm diversity, signaling and function. We anticipate that this research will pave new avenues for research on how diseases translate into infertility phenotypes or for the development of in vitro diagnostic tools.
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