Researchers led by Irv Weissman, director of the Ludwig Center at Stanford and Stanford’s Institute for Stem Cell Biology and Regenerative Medicine, and Lay Teng Ang of the Genome Institute of Singapore have mapped out the biological and chemical signals necessary to quickly and efficiently direct human embryonic stem cells to become pure populations of any of 12 cell types, including bone, heart muscle and cartilage. The ability to generate such cells within days, rather than the weeks or months previously required, is a key step toward regenerative medicine, which would permit the creation of new heart muscle to repair damage from a heart attack, or cartilage and bone to fix creaky joints and fractures. The study, published July 14 in Cell, also highlights short-lived patterns of gene expression that occur during human embryo segmentation and confirms that human development appears to rely on processes that are evolutionarily conserved among many animals. These insights may help elucidate how some congenital defects occur.
The researchers learned that cells often progress down the developmental path through a series of consecutive choices between two possible options. The quickest, most efficient way to micromanage the cells’ developmental decisions was to apply a simultaneous combination of factors that both encouraged the differentiation into one lineage while actively blocking a different fate—a kind of “yes” and “no” strategy. Carefully guiding the cells’ choices at each fork in the road, the researchers were able to generate bone cell precursors that formed human bone when transplanted into laboratory mice and beating heart muscle cells, as well as 10 other cell lineages derived from a layer of the human embryo known as the mesoderm. By looking at the gene expression profile in individual cells, the researchers identified previously unknown transient states that typified the progression from precursors to more specialized cells.