The first large-scale cellular map of gonadal development in both sexes has been created by researchers at the Wellcome Sanger Institute, as part of the Human Cell Atlas initiative to map all cell types in the human body.
Image credit: Khader Lab/Washington University School of Medicine
The findings, published in Nature, identified new cell types including those that express the ‘sex determination gene, beginning the process that decides whether an individual will become phenotypically male or female. The map will be transformative in improving the culture of gametes in fertility treatments and understanding reproductive conditions, such as differences in sex development.
The gonads play a key role in human development. They determine biological sex before maturing into ovaries in females or testes in males, which produce the egg and sperm cells required for reproduction.
The early weeks of development are extremely dynamic, with cell types appearing and disappearing rapidly as their purpose is fulfilled. This makes it challenging to study the events that lead to sex determination and subsequent differentiation into testis- or ovary-specific cells. While most of our knowledge of gonadal development comes from mouse studies, it is uncertain how much of this knowledge can actually be translated to humans.
In this new study, researchers at the Wellcome Sanger Institute set out to create the first large-scale cellular map of gonadal development in both sexes, in order to characterize the route that cells take to become either a testis or an ovary during early life. They analyzed around half a million cells from human gonadal tissue using single-cell sequencing and spatial transcriptomics, covering weeks six to 21 of pregnancy1.
The team also generated a similar map in mice that they used to understand where human and mouse biology are the same or different. To date, this is the most detailed map of the developing gonads in terms of both time and space.
The combination of single-cell and spatial technologies enabled the researchers to identify not only which genes were expressed in individual cells, but also to understand the arrangement of the different cell types within the tissue and how cells talk to one another. This is key to deciphering how the developing gametes interact with their neighboring cells as they mature inside the gonads to become sperm or egg cells.
The team identified patterns of gene expression that are unique to humans and are not shared with mice. Notably, the researchers pinned down the cell type that is the first to express the ‘sex determination gene, which initiates the process to decide whether the undifferentiated gonad will become a testis or an ovary. Named Early Supporting Gonadal Cells (ESGCs), this cell type was found to peak around six weeks after conception. ESGCs are present in both humans and mice, yet their gene expression pattern is different in the two species.
Source: Sanger Institute