The first large-scale cell 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.
The findings, published today in Nature, have identified new cell types, including those that express the “sex determination” gene, beginning the process that decides whether an individual will phenotypically become 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 becoming ovaries in females or testicles in males, which produce the eggs and sperm necessary for reproduction.
The first few weeks of development are extremely dynamic, with cell types rapidly appearing and disappearing as their purpose is achieved. This makes it difficult to study the events that lead to sex determination and subsequent differentiation into testis- or ovarian-specific cells. While most of our knowledge of gonadal development comes from mouse studies, it is unclear to what extent this knowledge can actually be applied to humans.
In this new study, researchers from the Wellcome Sanger Institute set out to create the first large-scale cellular map of gonadal development in both sexes, to characterize the pathway that cells take to become a testis or ovary during early pregnancy. life. They analyzed approximately half a million cells of human gonadal tissue using single-cell sequencing and spatial transcriptomics, covering weeks six to 21 of pregnancy.
The team also generated a similar map in mice which they used to understand where human and mouse biology are the same or different. This is the most detailed map of developing gonads in time and space to date.
The combination of single-cell and space technologies has allowed researchers to not only identify genes expressed in individual cells, but also to understand the arrangement of different cell types in the tissue and how the cells talk to each other. This is essential for deciphering how developing gametes interact with their neighboring cells as they mature inside the gonads to become sperm or egg cells.
The team identified gene expression patterns that are unique to humans and not shared with mice. In particular, the researchers identified the type of cell that is the first to express the “sex determination” gene, which initiates the process of deciding whether the undifferentiated gonad will become a testis or an ovary. Called early support gonadal cells (ESGCs), this type of cell peaked about six weeks after conception. ESGCs are present in both human and mouse, but their gene expression pattern is different in the two species.
“Gonadal development is a complex process and it is only at single cell resolution that you begin to see all of the cell types involved in sexual differentiation and can reduce the time frame in which this process takes place. The characterization of early gonadal supporting cells and their role in initiating sex determination is an exciting discovery that will help researchers better understand this crucial period of human development,” says Dr. Luz Garcia-Alonso.
Another key finding was specific populations of macrophages, a type of immune cell, in the testes. One of these populations resembled the macrophages found in the brain, while another resembled those found in the bones.
“It was fascinating to find populations of macrophages in gonads that we are used to seeing in other organs, given the very different purposes of the testes, brain, and bone. However, drawing parallels between the immune needs of each organ can help us understand the role of these macrophage populations wherever they are in the body.In terms of evolution, if you have a biological function that could be useful elsewhere, why not? ‘use”, explains Valentina Lorenzi.
One of the applications of this data will be to better understand differences in sex development (DSD). Although DSD has recently made headlines in sports, it encompasses a wide range of situations where a person’s chromosomal, gonadal, or anatomical sex is atypical. The team’s effort to extract the human-specific gene expression patterns of cell types appearing early in gonadal development will prove instrumental in improving the management of DSD.
“This large-scale cell map of gonadal development is a valuable addition to the Human Cell Atlas initiative that will enable research in this intriguing and complex area of human biology. I expect these data to further our understanding of the differences in sexual development, infertility and reproductive diseases,” explains Dr. Roser Vento-Tormo.
Deletion of the ‘Wt1’ gene produces alterations in the reproductive organs of mice
Luz Garcia-Alonso et al, Single-cell roadmap of human gonadal development, Nature (2022). DOI: 10.1038/s41586-022-04918-4
Provided by Wellcome Trust Sanger Institute
Quote: Cell map of human gonads identifies cells involved in sex determination (2022, July 7) Retrieved July 7, 2022 from https://phys.org/news/2022-07-cell-human-gonads-cells- involved.html
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