COLLEGE PARK, Md. – A UMD-led, multi-institution team of researchers has discovered new mechanisms that dictate the development of germline cells — precursor stem cells that become either eggs or sperm depending on whether they end up in ovaries or testes. Their findings ultimately could help advance research to combat cancers, viral diseases, male infertility and other health issues.

Stem cells, types of undifferentiated cells that have the ability to develop, or differentiate, into specific cell types such as egg, sperm, muscle or nerve cells, are at the forefront of new knowledge for understanding and fighting diseases. However, the mechanisms by which stem cells, and particularly germ cells, differentiate are still incompletely understood.  Germ cells are the only cell type capable of passing genetic information on to the next generation.

Published in Stem Cell Reports, the new study examined in chicken germ cells, mechanisms that factor into germ cell development and gene expression. In particular, it looked at DNA methylation, an essential mechanism for environmental (epigenetic) impacts on cell differentiation. UMD Professor Jiuzhou Song, Ph.D., department of animal and avian sciences, College of Agriculture and Natural Resources, and colleagues uncovered DNA methylation patterns associated with genes responsible for cancers and viral infections. 

Also discovered were markers in chickens used to identify male germ cells, uncovering how environmental factors-- epigenetics--affect these cells and providing significant insight into causes of and possible treatments for, male infertility in animals, including humans. These findings unlock possibilities for future animal and human health research in these areas, and also set the stage for chickens as a more prominent model organism for stem cell research. 

Stem cell research has applications for treating cancer, heart disease, neurological disorders like Alzheimer’s disease, diabetes, and even injuries. These cells can replicate and replace damaged tissue, so understanding their development is important to the future of this work. Epigenetic factors that affect the way genes are expressed, can also play a large role in cell and tissue development, and no studies have previously looked at the mechanisms at play in germline stem cell development and how epigenetics play a role. 

“From genome to phenome as it is called is a very complicated process for different gene networks to create the trait you see in an animal or human. The activity of key genes is the same or similar in common cell types, but the activity of other genes may differ completely among species, especially for the roles of stem cells,” explained Professor Songs. “Looking at these mechanisms helps to decode genes, understand complex traits, and develop future treatment plans to better understand animal and human health.”

The epigenetic markers identified in this study are unique to chickens, which are an up-and-coming animal model that is in many ways ideal for the study of epigenetics, stem cells, and developmental research.

“Most people still think of mice when they think of animal models that support animal and human health research. But regulatory elements are quite similar between the chicken and human genome. In fact, the genetic similarity between a human and a chicken is about 60%. The development of chickens is rapid, easy to see, and easy to manipulate, making them very unique compared to other animal models. They are ideal for developmental and stem cell research because you can easily observe egg growth and the development process in real time,” says Song.

Song said he is devoted to this animal genetics work, with its connections to human health in mind, but is also thinking about the broiler chicken industry and overall animal welfare. “This work provides a deeper understanding of developmental mechanisms in chickens that lead to healthier chickens and humans,” said Song. “The applications and need for epigenetic stem cell research is great, and chickens are a great model for this work.” 

COLLEGE PARK, Md. – A UMD-led study published in the journal Science sheds new light on how plants communicate within cells using a protein that closely resembles a protein that in animals plays a role in communications between nerve cells.

Although plants lack a true nervous system, previous studies have shown that plants need these proteins, called glutamate receptor-like proteins (GLRs), to do important things such as mate, grow, and defend themselves against diseases and pests.

In the current study, researchers working with pollen cells from a flowering weed native to Europe, Asia and Africa (Arabidopsis thaliana), found that these GLR proteins form the basis of a complex communication network inside individual plant cells. 

The research, which could inform many new studies of cell-to-cell communication in plants and animals alike, is featured on the cover of the May 4, 2018, issue of Science. Researchers from the University of Maryland, the Instituto Gulbenkian de Ciência in Portugal and the Universidad Nacional de Autónoma de México authored the study.

The similarities between the animal nerve proteins (glutamate receptors) and the similar GLR plant proteins suggests that the two proteins date back to a common ancestor—a single-celled organism that gave rise to both animals and plants.

“Why should plants have receptors like the ones that make neurons work? Our results support the idea that individual plant cells have a level of autonomy that animal cells do not,” said José Feijó, a professor of cell biology and molecular genetics at UMD and the senior author of the study. “Each plant cell has its own immune system, for example. And they have more communication channels to deal with the fact that they are stuck in place. Every flowering plant has more GLRs than animals have glutamate receptors. Our proposed model for plant cell communication suggests one reason for this abundance of GLRs.” 

Further progress toward decoding plant communication could result in reliable tests to diagnose diseases, nutrient deficiencies and other maladies in plants, Feijó said. Such measures could help to ensure food security, as climate change and other stressors begin to take a toll on major agricultural crops. 

Elaborating a two-protein process

The new findings suggest that GLRs rely on another group of proteins, called “cornichon” proteins, to shuttle GLRs to different locations in plant cells and to regulate activity of the protein within each cell.

With the help of cornichon proteins, GLRs act as valves that carefully manage the concentration of calcium ions—a vital aspect of many cell communication pathways—within various structures inside the cell, the study found. 

“Calcium concentration is one of the most important parameters inside all cells. It is so well regulated that it allows cells to encode information. Put another way, calcium is the lingua franca of cell communication,” said Feijó, noting that calcium is also vital to the function of animal neurons. “Our results suggest that GLRs play a role in this basic communication system in plants, and we also propose a mechanism for how the system works in plant cells.”

Feijó noted that there are some important differences between GLRs and their counterparts in animal neurons. 

To begin with, glutamate—the most common neurotransmitter in the human brain—does not play a major role in the plant system. Also, while glutamate receptors are known to sit on the outer surface of animal neurons, some of Feijo’s earlier experiments suggested that GLRs might instead be located on various structures inside plant cells. 

“This would be the only way to consistently explain the results we were getting,” Feijó said. “Our results suggest that GLRs are indeed redistributed to other compartments inside plant cells, forming a complex network that cooperates to regulate calcium concentrations and enable calcium signaling. This is a novel insight that opens completely new avenues to understand calcium signaling in plants.”

Feijó and Michael Wudick, a postdoctoral researcher in cell biology and molecular genetics at UMD and lead author of the paper, suspected that plant cells use a specific mechanism to control the locations of GLRs throughout the cell. This led Wudick to investigate cornichon proteins, which are linked to the activity of glutamate receptors in animals. 

In their experiments with Arabidopsis pollen cells, Feijó’s team found that cornichon proteins actively shuttled GLRs from one location to another within the cell, enabling various compartments inside the cell to maintain different calcium ion concentrations. Cornichons also act as gatekeepers for GLRs, switching the receptor molecules off and on like a valve in response to changing conditions inside the cell. 

Feijó also noted that a deeper understanding of GLRs could reveal new insights into animal glutamate receptors and their defects, which could be the cause of some neurodegenerative conditions. 

“Some researchers have suggested that neurodegeneration is caused by over-active glutamate receptors. This is not settled, but there are some conditions in both humans and dogs that have been linked to mutations in glutamate receptor genes,” Feijó said. “It is possible that our model could help investigate these conditions. The advantage is that our protocol is very easy to use.”

This work was supported by the U.S. National Science Foundation (Award Nos. MCB 1616437/2016 and MCB 1714993/2017), the Fundação para a Ciência e a Tecnologia (Award Nos. PTDC/BEX-BCM/0376/2012, PTDC/BIA-PLA/4018/2012, SFRH/PD/70739/2010 and SFRH/PD/70820/2010), the Consejo Nacional de Ciencia y Tecnología (Award No. 220085), and the Dirección General de Asuntos del Personal Académico-Universidad Nacional Autónoma de México (Award No. IN-203817). The content of this article does not necessarily reflect the views of these organizations.