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ÂÂ 2010-01-28, 11:29 PM #5
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https://www.hsc.virginia.edu/intern...m-stem-cell.cfm

RESEARCHERS DEVELOP SPERM STEM CELL LINE

Researchers have immortalized a stem cell line from the testis and used it to reproduce in culture several of the stages of sperm development, according to a study published in Science as part of Science Express web site on June 20. In a collaborative study, researchers from Georgetown University Medical Center, University of Virginia School of Medicine and Northwestern University have developed a mouse cell line capable of spermatogenesis, the process of sperm cell development.

The cell line replicates and differentiates in a tissue culture dish providing an in vitro system for scientists to study sperm differentiation. Among other uses, the cell line will provide a novel tool to identify and characterize the molecular cues required for sperm differentiation.

Previous efforts to create a cell line with the capacity to undergo spermatogenesis in vitro have been unsuccessful, impeding research in the field. It's a barrier to research progress that has been recognized for at least fifteen years, said John C. Herr, professor of cell biology at the University of Virginia School of Medicine and co-investigator of the study. The understanding of gene regulation during spermatogenesis has been delayed because much of the current work has to be done in transgenic animals.

Spermatogenesis is an ordered sequence of molecular signals that results in dramatic cellular changes contributing to the formation of a sperm cell. During this sequence of events, spermatogonia, the immature stem cells in the testis, divide and replicate. Next, a subset of spermatogonia progress into primary and secondary spermatocytes. This developmental step is characterized by meiosis, a specialized cell division process, which decreases the genetic material in the cell.

The secondary spermatocytes undergo another round of meiosis to become spermatids, which further progress through morphological changes and become mature sperm cells. The structural changes of the cellular architecture observed during spermatogenesis underscores the complex molecular signals required for this biological process, Herr said.

In this study, spermatogonia were immortalized after expressing the catalytic component of telomerase, TERT. Telomerase is an enzyme involved in DNA replication and the expression of TERT has led to the immortalization of other cell types. After one year the immortalized spermatogonial cells still shared the physical and molecular characteristics of spermatogonia.

To be useful as a model to study spermatogenesis, the cell line must also have the capacity to differentiate like spermatogonia in vivo, Herr said. In the body, stem cell factor (SCF), a protein ligand that activates a receptor on the surface of spermatogonia, initiates a signaling cascade that triggers the differentiation of the spermatogonia. As spermatogonia in vivo, the spermatogonial cell line treated with SCF underwent two meiotic divisions giving rise to primary and secondary spermatocytes and eventually spermatids.

Although tails or flagella, a characteristic of mature sperm, were not seen, various cells had structural features and biomarkers of spermatids. The novel cell line, established from primary mouse spermatogonial cells, displayed matching characteristics of spermatogonial stem cells as they could divide and differentiate in response to the ligand SCF.

A cell line has been developed that persists in culture and can be triggered with the appropriate stimulation to express markers of early spermatids, Herr said. The availability of a cell line that recapitulates at least part of the spermatogenesis process opens several new avenues for discovery. We can now isolate some of the factors involved in stage specific differentiation events during spermatogenesis.

For a field of research that was once hindered because of the absence of an experimental in vitro model, these findings will prove to be a valuable tool for understanding the intricate progression of spermatogenesis and provide opportunities to transplant genetically altered cells into host animals. It also may lead to strategies to perform gene therapies on the germ line, Herr said.

June 20, 2002

ÂÂ 2010-01-29, 02:25 AM #8
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ÂÂ 2010-01-29, 02:29 AM #9
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roma
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