Flatworms may not have the brain power of humans, but their regenerative capabilities have helped U researchers further understand fundamental functions of stem cells.
The work on the stem cells of flatworms could help scientists learn how to generate specific cell types to help with treatments of diseases ranging from degenerative disorders to cancer.
Alejandro Sánchez Alvarado, a neurobiology and anatomy professor, started working with flatworms 10 years ago. The aim of his research is to study the basic biology of animal stem cells, particularly those capable of producing the differentiated cells of all tissue types, such as with nerves and muscles.
“You have one stem cell, a cell that when it divides, for example, produces a duplicate of itself and another cell that goes on to differentiate,” said Sánchez Alvarado, a Howard Hughes Medical Institute investigator. “Immediately after division, the resulting cells are indistinguishable from each other.”
Researchers have not been able to tell the difference between the cells produced after cell division in flatworms. But through a marking system that could experimentally distinguish between the two, Sánchez Alvarado and two of his graduate students found more than 200 genes that can label the stem cells and those that will go on to produce differentiated cell types.
“We found sets of genes that specifically marked one or the other undifferentiated cells produce by cell division,” Sánchez Alvarado said. “One set of genes marks the stem cells proper, which will go on to divide, while the other set of genes marks the remaining undifferentiated cells that will eventually produce specific differentiated cell types.”
George Eisenhoffer, a neurobiology and anatomy graduate student, said now they know how to distinguish between the stem and non-stem cells, and they can begin to look at how animals produce a certain number and type of cells.
“We basically propose that because (flatworms) share similar aspects to human biology, what we learn here may be applicable to how stem cells operate in our bodies,” he said.
Eisenhoffer and Hara Kang, another neurobiology and anatomy graduate student working in Sánchez Alvarado’s lab, generated a series of techniques to look at the molecules operating in specific types of cells.
“Hara Kang developed tools to examine the cell cycle status of the (flatworm) stem cells,” Eisenhoffer said. “I used this methodology to characterize the different cell types identified in our analyses.”
He said the marking technique allows them to tag, or tattoo, the cells to distinguish between them.
Sánchez Alvarado said most of the research was done in the live flatworm instead of looking through a petri dish.
“Eisenhoffer carried out the majority of the experiment,” he said. “I came up with the idea for the work, and we went back and forth with ideas.”
Flatworms were specifically useful in this type of experiment because of the larger number of stem cells they have.
Flatworms have 15 to20 percent of stem cells in their body. Of all the cells humans have in their bodies, less than a fraction of a percent of them are stem cells.
Eisenhoffer and Kang are completing their doctoral thesis work partly based on this research, but the work is far from over.
“Now that we can identify one type of cell from another, we can perturb the decision-making process and identify genes specifically involved in deciding which cell type these undifferentiated cells will turn into in the living organism,” Sánchez Alvarado said.
With the tools to identify each cell before they change, researchers may be able to determine when genes begin to cause cancer, for example.
Sánchez Alvarado said a possible practical application down the road is to force a stem cell to go into one cell type versus another in vivo to produce a specific cell that the body may need.
The study was published in the September issue of Cell Stem Cell.
Lucas IsleyGeorge Eisenhoffer Jr., a Doctoral Candidate at the U, hopes that researching flatworms will hold keys on how to generate cells for treating degenerative disorders.