The discovery of a new kind of stem cell challenges conventional thinking about embryonic development. According to the traditional view, the human embryo develops from a three-layered collection of stem cells, with stem cells from different layers differentiating to form mature cells of different kinds. This view, however, is coming into question now that researchers have found stem cells capable of seizing fates once thought beyond their reach.

Researchers based at Mount Sinai report that they have found a type of stem cell that can become either a liver cell or an endothelial cell, that is, a cell that lines liver blood vessels. This finding is unexpected because the traditional view holds that liver cells and endothelial cells are supposed to emerge from different germ layers.

The long-held consensus was that an embryo develops to form the endoderm, the mesoderm, and the ectoderm. The endoderm goes on to form the liver and other gut organs; the mesoderm, the heart, muscles and blood cells; and the ectoderm, the brain and skin. Researchers have sought to determine the germ layer that yields each organ because these origins hold clues to healthy function and disease mechanisms in adults.

“We found a stem cell that can become either a liver cell, which is thought to originate in the endoderm, or an endothelial cell that helps to form a blood vessel, which was thought to derive from the mesoderm,” said Valerie Gouon-Evans, Ph.D., assistant professor in the Department of Developmental and Regenerative Biology and Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai. “Our results go against traditional germ layer theory, which holds that a stem cell can only go on to become cell types in line with the germ layer that stem cell came from. Endothelial cells may arise from both the endoderm and mesoderm.”

The Mount Sinai’s team’s discovery was were described in the October 15 print edition of Stem Cell Reports, in an article entitled, “Endoderm Generates Endothelial Cells during Liver Development.”
“We demonstrate that during development of the liver, which is an endoderm derivative, a subset of [endothelial cells] is generated from FOXA2+ endoderm-derived fetal hepatoblast progenitor cells expressing KDR (VEGFR2/FLK-1),” the authors wrote. “Using human and mouse embryonic stem cell models, we demonstrate that KDR+FOXA2+ endoderm cells developing in hepatic differentiation cultures generate functional [endothelial cells].”

The authors speculate that their finding may have implications for cancer research. Specifically, the discovery of a bi-potential progenitor cell advances the understanding of stem cell differentiation in fetal liver tissue, the hallmark of which is rapid growth, which is in some respects similar to the growth seen in tumors. Among the factors that make both possible is the building of blood vessels that supply nutrients and oxygen.

If similar bi-potential progenitor cells are found in liver cancers, they may be ideal targets for drugs that eradicate not only their descendant liver cancer cells but also the formation of blood vessels that feed tumors.

The new study also has implications for the field of liver regeneration. The newly discovered stem cell type, the researchers found, is present in both human and mouse livers as a fetus develops. Moreover, it appears that these cells have a regenerative effect when transplanted into damaged mouse livers.

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