Three of the genes are particularly intriguing because they code for proteins similar to those known to regulate mammalian embryonic stem cells. Such genetic similarity makes planarians an even more attractive model for studying stem cell biology in vivo.
RELEVANCE: Stem cells may hold the promise to regrow damaged, diseased, or missing tissues in humans, such as insulin-producing cells for diabetics and nerve cells for patients with spinal cord injuries. With its renowned powers of regeneration and more than half of its genes having human homologs, the planarian seems like a logical choice for studying stem cell behavior. Yet, until now, scientists have been unable to efficiently identify the genes that regulate the planarian stem cell system.
CAMBRIDGE, Mass. – Despite their unassuming appearance, the planarian flatworms in Whitehead Institute Member Peter Reddien's lab are revealing powerful new insights into the biology of stem cells—insights that may eventually help such cells deliver on a promising role in regenerative medicine.
In this week's issue of the journal Cell Stem Cell, Reddien and scientists in his lab report on their development of a novel approach to identify and study the genes that control stem cell behavior in planarians. Intriguingly, at least one class of these genes has a counterpart in human embryonic stem cells.
"This is a huge step forward in establishing planarians as an in vivo system for which the roles of stem cell regulators can be dissected," says Reddien, who is also an associate professor of biology at MIT and a Howard Hughes Medical Institute (HHMI) Early Career Scientist. "In the grand scheme of things for understanding stem cell biology, I think this is a beginning foray into seeking general principles that all animals utilize. I'd say we're at the beginning of that process."
Planarians (Schmidtea mediterranea) are tiny freshwater flatworms with the ability to reproduce through fission. After literally tearing themselves in half, the worms use stem cells, called cNeoblasts, to regrow any missing tissues and organs, ultimately forming two complete planarians in about a week.
Unlike muscle, nerve, or skin cells that are fully differentiated, certain stem cells, such as cNeoblasts and embryonic stem cells are pluripotent, having the ability to become almost cell type in the body. Researchers have long been interested in harnessing this capability to regrow damaged, diseased, or missing tissues in humans, such as insulin-producing cells for diabetics or nerve cells for patients with spinal cord injuries.
Several problems currently confound the therapeutic use of stem cells, including getting the stem cells to differentiate into the desired cell type in the appropriate location and having such cells successfully integrate with surrounding tissues, all without forming tumors. To solve these issues, researchers need a better understanding of how stem cells tick at the molecular level, particularly within the environment of a living organism. To date, a considerable amount of embryonic stem cell research has been conducted in the highly artificial environment of the Petri dish.
With its renowned powers of regeneration and more than half of its genes having human homologs, the planarian seems like a logical choice for this line of research. Yet, until now, scientists have been unable to efficiently find the genes that regulate the planarian stem cell system.
Postdoctoral researcher Dan Wagner, first author of the Cell Stem Cell paper, and Reddien devised a clever method to identify potential genetic regulators and then determine if those genes affect the two main functions of stem cells: differentiation and renewal of the stem cell population.
After identifying genes active in cNeoblasts, Wagner irradiated the planarians, leaving a single surviving cNeoblast in each planarian. Left alone, each cNeoblast can form colonies of new cells at very specific rates of differentiation and stem cell renewal.
The researchers knocked down each of the active genes, one per planarian, and observed how the surviving cNeoblasts responded. By comparing the rate of differentiation and stem cell renewal to that of normal cNeoblasts, they could determine the role of each gene. Thus, if a colony containing a certain knocked down gene were observed to have fewer stem cells than the controls, it could be concluded that gene in question plays a role in the process of stem cell renewal. And if the colony had fewer differentiated cells than normal, the knocked down gene could be associated with differentiation.
"Because it's a quantitative method, we can now precisely measure the role of each gene in different aspects of stem cell function," says Wagner. "Being able to measure stem cell activity with a colony is a great improvement over methods that existed before, which were much more indirect."
In total, Wagner identified 10 genes impacting cNeoblast renewal, and two genes with roles in both renewal and differentiation. According to Wagner, three of the stem cell renewal genes are particularly intriguing because they code for proteins that are similar to components of Polycomb Repressive Complex 2 (PRC2), known to regulate stem cell biology in mammalian embryonic stem cells and in other stem cell systems.
"It's interesting because it suggests a parallel between how stem cells operate in planarians and in mammals. For example, there might be similarities between how cNeoblasts and embryonic stem cells function and maintain stemness at the molecular level," he says.
This work was supported by the National Institutes of Health (NIH) and the Keck Foundation.
Written by Nicole Giese Rura
Peter Reddien's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a Howard Hughes Medical Institute Early Career Scientist and an associate professor of biology at Massachusetts Institute of Technology.Full Citation:
1. Howard Hughes Medical Institute, MIT Biology, Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
Nicole Giese Rura | EurekAlert!
Further reports about: > Biomedical > Cambridge > Medical Wellness > Stem cell innovation > Whitehead > cell biology > cell death > cell type > embryonic stem > embryonic stem cell > human embryonic stem cell > insulin-producing cell > molecular level > nerve cell > planarian > skin cell > spinal cord > spinal cord injuries > stem cell biology > stem cells
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction