The placental niche, a stem cell “safe zone,” supports blood stem cell generation and expansion without promoting differentiation into mature blood cells, allowing the establishment of a pool of precursor cells that provide blood cells for later fetal and post-natal life, said study senior author Dr. Hanna Mikkola, an associate professor of molecular cell and developmental biology and a researcher at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.
Mikkola and her team found that PDGF-B signaling in trophoblasts, specialized cells of the placenta that facilitate embryo implantation and gas and nutrient exchanges between mother and fetus, is vital to maintaining the unique microenvironment needed for the blood precursors. When PDGF-B signaling is halted, the blood precursors differentiate prematurely, creating red blood cells in the placenta, Mikkola said.
The study, done in mouse models, appears March 1, 2012, in the peer-reviewed journal Developmental Cell.
“We had previously discovered that the placenta provides a home for a large supply of blood stem cells that are maintained in an undifferentiated state. We now found that, by switching off one signaling pathway, the blood precursors in the placenta start to differentiate into red blood cells,” Mikkola said. “We learned that the trophoblasts act as powerful signaling centers that govern the niche safe zone.”
The study found that the PDGF-B signaling in the trophoblasts is suppressing production of Erythropoietin (EPO), a cytokine that controls red blood cell differentiation.
“When PDGF-B signaling is lost, excessive amounts of EPO are produced in the placenta, which triggers differentiation of red blood cells in the placental vasculature,” said Akanksha Chhabra, study first author and a post-doctoral fellow in Mikkola’s lab.
Mikkola and Chhabra used mouse models in which the placental structure was disrupted so they could observe what cells and signaling pathways were important components of the niche.
“The idea was, if we mess up the home where the blood stem cells live, how do these cells respond to the altered environment,” Chhabra said. “We found that it was important to suppress EPO where blood stem cell expansion is desired and to restrict its expression to areas where red blood cell differentiation should occur.”
The finding, Chhabra said, was exciting in that one single molecular change “was enough to change the function of an important blood stem cell niche.”
Mikkola said the blood stem cells expanded in the placental niche first seed the fetal liver and, ultimately, the bone marrow. The pool of blood stem cells could be compromised if the cells begin to differentiate in the placenta.
“We’ve been able to learn in the last few years about the niche cells in the adult bone marrow, but we didn’t know much about them during fetal development,” Mikkola said. “All hematopoietic niches in the embryo are unique in their own way, the stem cells are made in one location, expand in another and differentiate somewhere else. This is the first study that identifies a key niche cell and a signaling pathway in the placenta that allows it to do what it was destined to do, create a safe zone for the blood stem cells.”
The three-year study was funded by the National Institutes of Health, the California Institute of Regenerative Medicine, an Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Innovation Award and the Jonsson Cancer Center Foundation at UCLA.
“The discovery of PDGF-B signaling in the trophoblasts as an important regulator of local EPO levels in the placenta reveals a developmental stage and niche specific mechanism for regulating EPO expression, which is critical for governing the fates of blood stem cells during their developmental journey,” the study states. “This work gives new insights into the goal of recreating the different types of hematopoietic niches in vitro as well as furthers our understanding of the etiology of developmental defects originating from the placenta.”
The stem cell center was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research is committed to a multi-disciplinary, integrated collaboration of scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed towards future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine, UCLA’s Jonsson Cancer Center, the Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science. To learn more about the center, visit our web site at http://www.stemcell.ucla.edu. To learn more about the center, visit our web site at http://www.stemcell.ucla.edu.
Further reports about: > EPO > Gates Foundation > Medicine > Regenerative Therapien > Science TV > Stem cell innovation > blood cell > blood flow > blood stem cells > bone marrow > cell death > clinical application > embryonic stem cell > human embryonic stem cell > mouse model > placental > red blood cells > signaling pathway > stem cells
Superresolution live-cell imaging provides unexpected insights into the dynamic structure of mitochondria
18.02.2020 | Heinrich-Heine-Universität Düsseldorf
Blood and sweat: Wearable medical sensors will get major sensitivity boost
18.02.2020 | Moscow Institute of Physics and Technology
Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.
Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...
Investigation of the temperature dependence of the skyrmion Hall effect reveals further insights into possible new data storage devices
The joint research project of Johannes Gutenberg University Mainz (JGU) and the Massachusetts Institute of Technology (MIT) that had previously demonstrated...
Researchers at Chalmers University of Technology, Sweden, recently completed a 5-year research project looking at how to make fibre optic communications systems more energy efficient. Among their proposals are smart, error-correcting data chip circuits, which they refined to be 10 times less energy consumptive. The project has yielded several scientific articles, in publications including Nature Communications.
Streaming films and music, scrolling through social media, and using cloud-based storage services are everyday activities now.
After helping develop a new approach for organic synthesis -- carbon-hydrogen functionalization -- scientists at Emory University are now showing how this approach may apply to drug discovery. Nature Catalysis published their most recent work -- a streamlined process for making a three-dimensional scaffold of keen interest to the pharmaceutical industry.
"Our tools open up whole new chemical space for potential drug targets," says Huw Davies, Emory professor of organic chemistry and senior author of the paper.
Superconductivity approaching room temperature may be possible in hydrogen-rich compounds at much lower pressures than previously expected
Reaching room-temperature superconductivity is one of the biggest dreams in physics. Its discovery would bring a technological revolution by providing...
12.02.2020 | Event News
16.01.2020 | Event News
15.01.2020 | Event News
18.02.2020 | Power and Electrical Engineering
18.02.2020 | Information Technology
18.02.2020 | Physics and Astronomy