News | The Future of Germ Cells: Scientists Reprogram Cells in Marmosets
Primate Cells Reprogrammed into Germ Cell Precursors
Researchers at the University of Pennsylvania School of Veterinary Medicine, the University of Texas at San Antonio, and the Texas Biomedical Research Institute reprogrammed marmoset blood cells into flexible stem cells and guided them into cells with sperm-precursor characteristics. Published in eLife, the study represents an important advance in reproductive biology.
Paving the Way for Germ Cell Generation
The team reprogrammed cells through several stages into germ cell precursors. This creates new opportunities to study primate biology and supports development of assisted reproductive technologies such as in vitro gametogenesis, the laboratory production of sperm or eggs, similar to embryo generation in in vitro fertilization (IVF).
University of Pennsylvania assistant professor Kotaro Sasaki said scientists can generate functional sperm and eggs from induced pluripotent stem cells in mice, but mouse germ cells differ substantially from human germ cells. Marmosets offer a model closer to human biology.
Germ Cell Precursors in Marmoset Embryos
Researchers first studied primordial germ cells (PGCs) from marmoset embryos, which had not previously been rigorously characterized. They identified molecular markers that allowed the early cells to be tracked. Single-cell RNA sequencing showed expression of genes associated with early germ cells and epigenetic modification, but not genes activated later when sperm or egg precursors migrate to the ovaries or testes.
Dr. Sasaki said the findings were consistent with germ-cell reprogramming that switches off certain markers and allows PGCs to progress through later developmental stages.
From Blood Cells to Induced Pluripotent Stem Cells
The team then recreated the process in the laboratory, first converting blood cells into induced pluripotent stem cells (iPSCs), which can differentiate into other cell types. Postdoctoral researcher Yasunari Seita said establishing stable culture conditions for marmoset cells was the greatest challenge despite his experience with cell culture and iPSCs. After repeated experiments informed by mouse, human, and other studies, he developed a stable method for generating and maintaining marmoset iPSCs.
From iPSCs to Germ Cell Precursors
A mixture of growth factors converted 15%-40% of cultured cells into cells with germ-cell precursor characteristics. Dr. Sasaki said the efficiency allowed cultures to be expanded through multiple passages with strong exponential growth. The cells retained germ-cell markers but lacked other markers associated with migration to the gonads.
Modeling Sperm Precursor Development
In the final stage, laboratory-grown cells developed features of later germ cells. Building on the team's 2020 Nature Communications study, researchers cultured them with mouse testicular cells for one month. Some cells activated genes associated with later sperm precursors, indicating further development.
Outlook for In Vitro Gametogenesis
Dr. Sasaki noted that clinical use of in vitro gametogenesis involves ethical, legal, and safety questions. A robust preclinical model is needed before future human applications can be considered.
The study provides a new primate research model and a foundation for reproductive technologies. Continued marmoset research may also support advances in reproductive biology and neuroscience.
News | The Future of Germ Cells: Scientists Reprogram Cells in Marmosets
News | The Future of Germ Cells: Scientists Reprogram Cells in Marmosets
Primate Cells Reprogrammed into Germ Cell Precursors
Researchers at the University of Pennsylvania School of Veterinary Medicine, the University of Texas at San Antonio, and the Texas Biomedical Research Institute reprogrammed marmoset blood cells into flexible stem cells and guided them into cells with sperm-precursor characteristics. Published in eLife, the study represents an important advance in reproductive biology.
Paving the Way for Germ Cell Generation
The team reprogrammed cells through several stages into germ cell precursors. This creates new opportunities to study primate biology and supports development of assisted reproductive technologies such as in vitro gametogenesis, the laboratory production of sperm or eggs, similar to embryo generation in in vitro fertilization (IVF).
University of Pennsylvania assistant professor Kotaro Sasaki said scientists can generate functional sperm and eggs from induced pluripotent stem cells in mice, but mouse germ cells differ substantially from human germ cells. Marmosets offer a model closer to human biology.
Germ Cell Precursors in Marmoset Embryos
Researchers first studied primordial germ cells (PGCs) from marmoset embryos, which had not previously been rigorously characterized. They identified molecular markers that allowed the early cells to be tracked. Single-cell RNA sequencing showed expression of genes associated with early germ cells and epigenetic modification, but not genes activated later when sperm or egg precursors migrate to the ovaries or testes.
Dr. Sasaki said the findings were consistent with germ-cell reprogramming that switches off certain markers and allows PGCs to progress through later developmental stages.
From Blood Cells to Induced Pluripotent Stem Cells
The team then recreated the process in the laboratory, first converting blood cells into induced pluripotent stem cells (iPSCs), which can differentiate into other cell types. Postdoctoral researcher Yasunari Seita said establishing stable culture conditions for marmoset cells was the greatest challenge despite his experience with cell culture and iPSCs. After repeated experiments informed by mouse, human, and other studies, he developed a stable method for generating and maintaining marmoset iPSCs.
From iPSCs to Germ Cell Precursors
A mixture of growth factors converted 15%-40% of cultured cells into cells with germ-cell precursor characteristics. Dr. Sasaki said the efficiency allowed cultures to be expanded through multiple passages with strong exponential growth. The cells retained germ-cell markers but lacked other markers associated with migration to the gonads.
Modeling Sperm Precursor Development
In the final stage, laboratory-grown cells developed features of later germ cells. Building on the team's 2020 Nature Communications study, researchers cultured them with mouse testicular cells for one month. Some cells activated genes associated with later sperm precursors, indicating further development.
Outlook for In Vitro Gametogenesis
Dr. Sasaki noted that clinical use of in vitro gametogenesis involves ethical, legal, and safety questions. A robust preclinical model is needed before future human applications can be considered.
The study provides a new primate research model and a foundation for reproductive technologies. Continued marmoset research may also support advances in reproductive biology and neuroscience.
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