Inner origami

Imagining the individual fates of embryonic stem cells is like envisioning what will become of a class of kindergartners: It’s not obvious who will be a poet, a math whiz or a class clown.

Now, scientists studying therapies for a blistering skin disease believe they have narrowed down how proteins responsible for helping stem cells become distinct tissue types — like muscles, skin or nerves — team up to spark the process.

Their findings emerged during research on how stem cells develop into cells called keratinocytes to form sheets of skin. Replicating the process could help repair open wounds in people with epidermolysis bullosa, a genetic condition caused by mutations in the keratin protein that helps bind cells to form skin tissue. If tissue doesn’t bind properly, it falls apart and easily blisters from friction.

During the study, researchers identified a key regulatory hierarchy whereby proteins called morphogens control the origamilike folding and unfolding of the cell’s DNA. The process brings master regulators called transcription factors in contact with the set of genes necessary for skin development.

“For the first time, we were able to see how morphogens and master transcriptional regulators work together to make specific cell types,” said dermatologist Anthony Oro, MD, PhD, the Eugene and Gloria Bauer Professor. “We’ve always wondered how a transcription factor required for the production of vastly different cell types knows which genes to make into proteins in which situation.”

Now they know that morphogens help the master transcription factors hook up to the right targets and that specific cell development is not random.

“We can work to harness and accelerate this process to generate all kinds of transplantable tissues,” said Oro, senior author of a paper describing the research published Nov. 5 in Nature Genetics.