Scientists identify crucial cell and signaling pathway in placental blood stem cell niche

March 1, 2012 By Kim Irwin in Medical research

(Medical Xpress) -- UCLA stem-cell researchers have identified a certain type of cell and a signaling pathway in the placental niche that play a key role in stopping blood stem cells from differentiating into mature blood cells in the placenta. Preventing this premature differentiation is critical to ensuring a proper blood supply for an individual's lifetime.

The placental niche, a stem cell "safe zone," supports blood stem and expansion without promoting differentiation into mature blood , allowing the establishment of a pool of 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 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 and gas and nutrient exchanges between mother and fetus, is vital to maintaining the unique 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 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 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 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 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 ."

Provided by University of California - Los Angeles

5 /5 (1 vote)  

Rank 5 /5 (1 vote)
Relevant PhysicsForums posts

More news stories

Study suggests new source of kidneys for transplant

Nearly 20 percent of kidneys that are recovered from deceased donors in the U.S. are refused for transplant due to factors ranging from scarring in small blood vessels of the kidney's filtering units to the organ going too ...

Medical research created 16 hours ago | popularity 5 / 5 (2) | comments 0 | with audio podcast

Discovery of circadian clock in mice hair reveals period of time when damage from radiotherapy can be quickly repaired

Discovering that mouse hair has a circadian clock - a 24-hour cycle of growth followed by restorative repair - researchers suspect that hair loss in humans from toxic cancer radiotherapy and chemotherapy ...

Medical research created 16 hours ago | popularity 5 / 5 (2) | comments 1 | with audio podcast

Do salamanders hold the solution to regeneration?

Salamanders' immune systems are key to their remarkable ability to regrow limbs, and could also underpin their ability to regenerate spinal cords, brain tissue and even parts of their hearts, scientists have ...

Medical research created 17 hours ago | popularity 4.9 / 5 (7) | comments 3 | with audio podcast

New study finds blind people have the potential to use their 'inner bat' to locate objects

New research from the University of Southampton has shown that blind and visually impaired people have the potential to use echolocation, similar to that used by bats and dolphins, to determine the location of an object.

Medical research created 20 hours ago | popularity not rated yet | comments 1 | with audio podcast

Germ-fighting vaccine system makes great strides in delivery

A novel vaccine study from South Dakota State University (SDSU) will headline the groundbreaking research that will be unveiled at the American Association of Pharmaceutical Scientists' (AAPS) National Biotechnology Conference ...

Medical research created 20 hours ago | popularity not rated yet | comments 0


Sugar injections for knee arthritis may ease pain

(HealthDay)—Injections of a sugar solution appear to help relieve knee pain and stiffness related to osteoarthritis, a new study suggests.

Anti-CD47 antibody may offer new route to successful cancer vaccination

(Medical Xpress)—Scientists at the School of Medicine have shown that their previously identified therapeutic approach to fight cancer via immune cells called macrophages also prompts the disease-fighting killer T cells ...

Evaluating a new way to open clogged arteries

Over the past few decades, scientists have developed many devices that can reopen clogged arteries, including angioplasty balloons and metallic stents. While generally effective, each of these treatments ...

Losing weight may ease chronic heartburn

(HealthDay)—Obese and overweight men and women who suffer from heartburn often report relief when they lose weight, a new study shows.

Primary care docs should play role in kids' dental health, experts say

(HealthDay)—When it comes to the care of your children's teeth, dentists aren't the only experts who can help.

Study identifies superior hypertension treatment, efficacy between sexes

(Medical Xpress)—In a recent subgroup analysis of the largest blood pressure treatment trial in history, University of Alabama at Birmingham (UAB) researchers found that women and men react the same to ...