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UCLA stem cell researchers have discovered a critical placental niche cell andsignaling pathway that prevent blood precursors from prematuredifferentiation in the placenta, a process necessary for ensuringproper blood supply for an individual's lifetime. The placental niche, a stem cell "safe zone," supports blood stemcell generation and expansion without promoting differentiationinto mature blood cells, allowing the establishment of a pool ofprecursor cells that provide blood cells for later fetal andpost-natal life, said study senior author Dr. Hanna Mikkola, anassociate professor of molecular cell and developmental biology anda researcher at the Eli and Edythe Broad Center of RegenerativeMedicine and Stem Cell Research at UCLA. Mikkola and her team found that PDGF-B signaling in trophoblasts,specialized cells of the placenta that facilitate embryoimplantation and gas and nutrient exchanges between mother andfetus, is vital to maintaining the unique microenvironment neededfor the blood precursors. When PDGF-B signaling is halted, theblood precursors differentiate prematurely, creating red bloodcells in the placenta, Mikkola said. The study, done in mouse models, appears March 1, 2012, in thepeer-reviewed journal Developmental Cell. "We had previously discovered that the placenta provides a home fora large supply of blood stem cells that are maintained in anundifferentiated state. We now found that, by switching off onesignaling pathway, the blood precursors in the placenta start todifferentiate into red blood cells," Mikkola said. "We learned thatthe trophoblasts act as powerful signaling centers that govern theniche safe zone." The study found that the PDGF-B signaling in the trophoblasts issuppressing production of Erythropoietin (EPO), a cytokine thatcontrols red blood cell differentiation. "When PDGF-B signaling is lost, excessive amounts of EPO areproduced in the placenta, which triggers differentiation of redblood 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 placentalstructure was disrupted so they could observe what cells andsignaling pathways were important components of the niche. "The idea was, if we mess up the home where the blood stem cellslive, how do these cells respond to the altered environment,"Chhabra said. "We found that it was important to suppress EPO whereblood stem cell expansion is desired and to restrict its expressionto areas where red blood cell differentiation should occur." The finding, Chhabra said, was exciting in that one singlemolecular change "was enough to change the function of an importantblood stem cell niche." Mikkola said the blood stem cells expanded in the placental nichefirst seed the fetal liver and, ultimately, the bone marrow. Thepool of blood stem cells could be compromised if the cells begin todifferentiate in the placenta. "We've been able to learn in the last few years about the nichecells in the adult bone marrow, but we didn't know much about themduring fetal development," Mikkola said. "All hematopoietic nichesin the embryo are unique in their own way, the stem cells are madein one location, expand in another and differentiate somewhereelse. This is the first study that identifies a key niche cell anda signaling pathway in the placenta that allows it to do what itwas destined to do, create a safe zone for the blood stem cells." The three-year study was funded by the National Institutes ofHealth, the California Institute of Regenerative Medicine, an Eliand Edythe Broad Center of Regenerative Medicine and Stem CellResearch Innovation Award and the Jonsson Cancer Center Foundationat UCLA. "The discovery of PDGF-B signaling in the trophoblasts as animportant regulator of local EPO levels in the placenta reveals adevelopmental stage and niche specific mechanism for regulating EPOexpression, which is critical for governing the fates of blood stemcells during their developmental journey," the study states. "Thiswork gives new insights into the goal of recreating the differenttypes of hematopoietic niches in vitro as well as furthers ourunderstanding of the etiology of developmental defects originatingfrom the placenta." Additional References Citations. The e-commerce company in China offers quality products such as China Sheet Metal Components , Wire Storage Cage Manufacturer, and more. For more , please visit Wire Mesh Products today!
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