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
Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel
Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
26.04.2017 | Materials Sciences
26.04.2017 | Agricultural and Forestry Science
26.04.2017 | Physics and Astronomy