UCLA stem cell researchers have discovered a critical placental niche cell and signaling pathway that prevent blood precursors from premature differentiation in the placenta, a process necessary for ensuring proper blood supply for an individual’s lifetime.
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.”