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While humans can’t renew their reproductive cells and organs if damaged, many invertebrates can as part of whole-body regeneration. Understanding how and why could have major implications for human stem-cell research and, potentially, for infertility treatments.

Duygu Özpolat at the Marine Biological Laboratory (MBL) is tracing the lineage of regenerated reproductive cells—also called the germline—to determine the cellular programming that allows for their resurgence.

MBL Hibbitt Fellow B. Duygu Özpolat. Credit: Daniel Cojanu

“We are trying to understand where the cells that regenerate the germline come from,” says Özpolat. “Once we know that, we may be able to understand why some organisms can regenerate them and some can’t.” Özpolat is a Hibbitt Fellow in the ǧ����Ƶ’s Bell Center for Regenerative Biology and Tissue Engineering.

Now, Özpolat and her colleagues are a step closer to this goal.�� reveals that their research organism, the marine worm Platynereis dumerilii,��must develop a certain number of body segments before it starts forming its original reproductive cells.

“If you're going to study the regeneration of a structure in an organism, you need to know how that original structure formed first,” says Özpolat. “And before this study, we didn't have a good understanding of when that happens.”

The paper, published in , shows that progenitor reproductive cells develop in P. dumerilii when the worms reach between 35 and 40 segments. Before this discovery, researchers working with P. dumerilii would have to conduct time-consuming assays to determine if the worm had enough original reproductive cells to begin experimentation.

Led by Özpolat and first author Emily Kuehn, a research assistant in Özpolat’s lab, the researchers used a technique called in situ hybridization to locate the germline cells in the worm’s body and track their development as segments were added. They studied hundreds of the two-centimeter worms, carried out different interventions, and generated a wealth of data that led them to their remarkably consistent conclusion.

The Özpolat lab’s research organism, Platynereis dumerilii. Credit Ryan Null

“The most surprising thing for me was the reliability of this segment count and its correlation to development of the germline,” says Özpolat. Establishing this standard significantly cuts back on time and resources needed to study reproductive cell regeneration and increases reproducibility of data.

The team also published a first-of-kind algorithm to facilitate the use of a fluorescent in situ hybridization method in this type of experiment.

This research builds on years of work from the Özpolat lab. For example, the worms were cultured using a streamlined, scalable system developed in the lab and published in 2019. A standardized culturing system is key to understanding genetic cause and effect. If worms grow in different environments with different feeding schedules, it is nearly impossible to determine if variations observed in experiments are due to the scientists’ interventions or to growth conditions.

Özpolat and team will follow this research with investigations into what happens when germline cells are forced to regenerate. They will amputate 90 percent of the worms’ length and watch as the germlines reemerge. They will then track the function of those regenerated cells and their effect on the health of the next generation, versus control worms who reproduce without being forced to regenerate germline cells.

“Right now, the thing that we are most curious about is, do the progeny that come from a regenerated germline have more mutations?” says Özpolat. “And, if so, how do those mutations affect the fitness of the next generation?”

Understanding the cellular and molecular pathways involved in regeneration could help Özpolat and her team understand how to make it happen in humans.

“Way down the line, this could inform infertility treatments,” says Özpolat. “Our job in fundamental science is to learn how these worms do cellular reprogramming. And if they keep the mutations at the low level, how they do that? Then maybe we can apply that to human therapies for regenerating cells or reprogramming cell types from different body parts.”

Citation:

,��,��,��,��,�� (2021) Segment number threshold determines juvenile onset of germline cluster expansion in Platynereis dumerilii.��Journal of Experimental Zoology Part B: Molecular and Developmental Evolution, DOI: 

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The Marine Biological Laboratory (MBL) is dedicated to scientific discovery – exploring fundamental biology, understanding marine biodiversity and the environment, and informing the human condition through research and education. Founded in Woods Hole, Massachusetts in 1888, the ǧ����Ƶ is a private, nonprofit institution and an affiliate of the .