Researchers have demonstrated the ability to program groups of individual cells to self-organize into multi-layered structures reminiscent of simple organisms or the first stages of embryonic development. A complex biological structures, an eye, a hand, a brain emerge from a single fertilized egg. This is the fundamental question of developmental biology, and a mystery still being grappled with by scientists who hope to one day apply the same principles to heal damaged tissues or regrow ailing organs. The study was published in Science.

A few simple forms of collective cell communication were sufficient to cause ensembles of cells to change color and self-organize into multi-layered structures akin to simple organisms or developing tissues. In their simplest experiment of this sort, the researchers programmed two groups of cells to self-organize into a two-layered sphere. They started with one group of blue cells expressing a signaling protein on their surfaces, and a second group of colorless cells sporting a custom synNotch receptor programmed to detect this signal protein.

When isolated from one another, these cell populations did nothing, but when the two groups were mixed, the blue cells activated the synNotch receptors on the clear cells and triggered them to produce sticky cadherins and a green marker protein called GFP. As a result, the colorless cells quickly began to turn green and cluster together, forming a central core surrounded by an outer layer of their partner blue cells.

The researchers went on to program groups of cells to self-assemble in increasingly complex ways, such as building three-layered spheres or starting with a single group of cells that sorted themselves into two distinct groups before forming a layered sphere.

They even engineered cells that formed the beginnings of "polarity" the distinct front-back, left-right, head-toe axes that define the "body plans" of many multicellular organisms by expressing different types of cadherin adhesion molecules that instructed the cellular assemblages to divide into "head" and "tail" sections or to produce four distinct radial "arms."

In the future, Lim imagines programming ever more complex tissue-like cellular structures through multiple layers of synNotch signaling.

These more complex cellular programming feats demonstrated that simple starter cells could be programmed to develop over time to form more complex structures, much like a single fertilized egg divides and differentiates to form different parts of the body and distinct tissues like skin, muscle, nerve, and bone.

Research team showed that these complex spheroids were also self-repairing: when the researchers cut the multi-layered spheroids in half with a micro-guillotine developed, the remaining cells quickly re-formed and reorganized themselves according to their intrinsic program.

The author hopes his lab's work will help guide scientists towards being able to program stem cells to repair damaged tissue, or even build new organs that grow with the right connections to the rest of the body. If they could grow a new organ directly in the body so that it specifically grows connected to the right places.