Rewired marmoset blood cells give rise to precursors of sperm

March 03, 2023 | Biotechnology

Experts from the University of Pennsylvania School of Veterinary Medicine, University of Texas at San Antonio and Texas Biomedical Research Institute, have repurposed marmoset blood cells to have the flexibility of stem cells. They later on directed these stem cells to assume the characteristics of sperm precursors. This opens for a wide range of possibilities - exploring primate biology and in refining novel assisted reproductive technologies, such as in vitro gametogenesis.

Kotaro Sasaki, assistant professor at Penn Vet., said that although functional sperm and egg can be produced from induced pluripotent stem cells in mice, mouse germ cells are too distinct from human germ cells. In examining marmosets, scientists can bridge that gap as its biology closely resembles that of ours, making it a valuable model for reproductive biology studies.

The research team performed single-cell RNA sequencing on primordial germ cells (PGCs) from marmoset embryos, which have molecular markers that could be traced over time. It revealed that PGCs expressed genes that characterize epigenetic modifications. However, it did not express genes that would turn on later during the process of germ cell development, a time where precursor cells move to the ovaries and testes for complete maturation.

These findings support the notion that marmoset cells go through a reprogramming process that turns off molecular markers, allowing PGCs to proceed through the process of development.

With these, the team went on reconstituting the development process artificially. They first transformed blood cells into induced pluripotent stem cells (iPSCs) in order to retain the ability of giving rise to a number of other cell types. Establishing a strategy for sustaining a stable culture for iPSCs required much trial and error. Key was to add an inhibitor of the signaling pathway controlled by the Wnt protein. The second stage is moving from iPSCs to germ cell precursors. This involved adding a variety of growth factors to prompt the culture to acquire the characteristics of germ cell precursors. The final stage is coaxing the lab-grown cells to assume later-stage germ cell characteristics.

Since clinical applications for assisted reproductive technologies usually have a lot of ethical, legal, and safety concerns, the need for a good preclinical model before proceeding to human clinical translation is a must. Marmosets presents a new avenue for studies that focus on normal and abnormal development in fertility.