Marmoset Blood Cells Transformed into Sperm Cell Precursors

Researchers from the University of Pennsylvania School of Veterinary Medicine, along with collaborators from the University of Texas at San Antonio and Texas Biomedical Research Institute, successfully transformed marmoset blood cells into induced pluripotent stem cells (iPSCs) and then into germ cells, or sperm precursors, in a laboratory dish. The process of in vitro gametogenesis enables germ cell generation outside the human body, offering new possibilities for biological research and the development of novel assisted reproductive technologies.

The scientists first studied primordial germ cells (PGCs) from marmoset embryos, which had never been rigorously characterized for the species. They found that these early-stage cells bore specific molecular markers that could be tracked over time. Performing single-cell RNA sequencing on these cells revealed that PGCs expressed genes characteristic of early-stage germ cells and those related to epigenetic modifications, which regulate gene expression. PGCs did not, however, express genes known to be turned on later in the process of germ cell development when precursor cells migrate to the ovaries or testes to complete their maturation.

With that information in hand, the team tried to reconstitute this process in the lab. The first step was transforming blood cells into iPSCs. After much trial and error, and applying lessons learned from mouse, human, and other investigations of model organisms, the team generated and sustained stable cultures of iPSCs.

The next step was to develop protocol that effectively transitioned from iPSCs to germ cell precursors. Utilizing a cocktail of growth factors, the team successfully prompted between 15-40% of their culture to take on the characteristics of these germ cell precursors.

In the final stage of the study, the research team coaxed these lab-grown cells to take on the characteristics of later-stage germ cells. Based on a pre-existing method for human cells, the team cultured cells with mouse testicular cells over a month. The results were successful, with some cells beginning to turn on genes associated with later-stage sperm cell precursors.

Scientists can bridge the gap between mice and humans by studying marmosets, whose biology closely resembles humans, to create an effective preclinical model before moving to human clinical translation. The ability to generate functional sperm and egg from iPSCs provides an opportunity to understand the molecular underpinnings of germ cell development.

Developing new approaches to examining marmosets encourages the scientific community to utilize this species as an important research model, leading to new discoveries relating to neuroscience, development, and fertility.