Researchers at ChristianaCare and UD uncover possible “Tissue Code” behind how human bodies stay organized

Gary Schleiniger, Ph.D., and Bruce Boman, M.D., Ph.D., longtime collaborators behind the study, uncovered potential rules of tissue organization. (Photo courtesy ChristianaCare)

Researchers from ChristianaCare’s Helen F. Graham Cancer Center & Research Institute and the University of Delaware have uncovered what may be a fundamental set of rules that keep human tissue organized, even as the body replaces billions of cells every day.

In a recent study published in the scientific journal Biology of the Cell, researchers demonstrate how five simple rules can govern the precise structure and behavior of tissues like the colon, offering what they describe as a possible “tissue code.”

“This may be the biological version of a blueprint,” said Bruce Boman, M.D., Ph.D., senior research scientist at ChristianaCare’s Cawley Center for Translational Cancer Research and a faculty member in the departments of Biological Sciences and Mathematical Sciences at the University of Delaware.

“Just like we have a genetic code that explains how our genes work, we may also have a ‘tissue code’ that explains how our bodies stay so precisely organized over time,” he said.

The breakthrough comes after more than 15 years of collaboration between cancer biologists and mathematicians who developed computer simulations to model cell behavior. They focused on the human colon, where cells regenerate every few days yet maintain a stable, functional structure.

Using mathematical modeling, the team identified five core rules:

Timing of cell division
The order in which cells divide
The direction cells divide and move
How many times cells divide
How long a cell lives before it dies

“These rules work together like choreography,” said Gilberto Schleiniger, Ph.D., professor in the University of Delaware’s Department of Mathematical Sciences. “They control where cells go, when they divide and how long they stick around — and that’s what keeps tissues looking and working the way they should.”

The research suggests that these rules may apply broadly across different tissues in the body — from skin and liver to brain tissue — and could help scientists better understand processes such as wound healing, developmental disorders, and cancer.

“Tissues don’t just grow and shrink randomly. They know what they’re supposed to look like, and they know how to get back to that state, even after damage,” Boman said. “That level of precision needs a set of instructions. What we’ve found is a strong candidate for those instructions.”

Computer-generated image showing how cells in the human colon renew and organize over time, based on mathematical modeling. (Photo courtesy ChristianaCare)

These insights may also support global scientific efforts such as the Human Cell Atlas, which aims to map every cell type in the body. While the Atlas catalogs what cells are doing at a given moment, this new research provides a framework for understanding how they maintain organization over time.

The team’s use of mathematical modeling, rather than traditional lab experiments, allowed them to simulate and analyze behaviors that are difficult to observe in real time.

“This is just the beginning,” Schleiniger said. “Once you can identify the rules, you can begin to ask entirely new questions, and maybe even learn how to fix what’s gone wrong.”

The study aligns with the National Science Foundation’s “Rules of Life” initiative, which seeks to uncover basic principles that govern living systems. The next phase of the project includes experimental testing of the model’s predictions and further exploration of how disruptions in the tissue code might contribute to cancer development or metastasis.

The National Institutes of Health, the National Science Foundation, the Lisa Dean Moseley Foundation, the Delaware Bioscience Center for Advanced Technology, and the UNIDEL Graduate Research Fellowship provided funding for the research.