Researchers Discover Five Simple Rules That May Explain How Tissues Stay Organized

Cell division and tissue organization are at the heart of how the human body repairs itself and maintains structure, even as billions of cells are replaced daily. But what governs this remarkable precision? A new study reveals five simple yet powerful rules that may explain how tissues in the body stay organized, offering major implications for cancer biology, tissue repair, and computational systems.

A collaborative team of scientists from ChristianaCare’s Helen F. Graham Cancer Center & Research Institute and the University of Delaware has proposed a potential “tissue code”—a blueprint that regulates the behavior of cells across tissues in the body. Their research, published in Biology of the Cell, represents over 15 years of collaboration between cancer research experts and computational biologists.

The Mathematics Behind Tissue Architecture

Focusing on the colon—a tissue known for its rapid cell division—the team used computational biology and advanced modeling techniques to simulate how cells divide, move, and die while maintaining structure. They identified five core rules:

1. Timing of cell division
2. Sequence of cell division
3. Direction of division and cell movement
4. Number of cell divisions per cell
5. Lifespan of each cell
   

“These rules act like choreography,” said Dr. Gilberto Schleiniger, the study’s lead mathematician. “They determine when a cell should divide, how far it should move, and when it should die ensuring consistent tissue structure despite constant renewal”.

A Universal Code for Tissues?

While the study centered on the colon, researchers believe this tissue code could apply broadly to human body tissue, including skin, liver, and brain. If validated, it may explain how tissue healing stages unfold after injury, or what happens when errors in this code lead to cancer or developmental disorders.

“It’s like a biological instruction manual,” explained Dr. Bruce Boman, a leading cancer research scientist on the team. “Where DNA gives genetic commands, the tissue code may guide structure through cell division stages and regulated behavior.”

Enhancing the Human Cell Atlas

This discovery also offers a dynamic layer to large-scale mapping efforts like the Human Cell Atlas, which aims to document every cell in the human body. While the Atlas shows what each cell is doing, this model explores how cells behave collectively over time.

By identifying universal rules that govern cell division and cell cycle behavior, the study lays the groundwork for predicting disruptions that cause disease and potentially guiding tissue repair at a systems level.

Computational Biology Meets Cancer Research

The team used mathematical modeling because it’s nearly impossible to track every living cell in real-time. This strategy reflects a broader shift in cancer research technology, where computational biology plays a key role in decoding complex biological behavior.

Their work is part of the National Science Foundation’s “Rules of Life” initiative, aiming to identify key principles of living systems. Future research will use experimental data to validate the model—and to explore how breaking these five rules may contribute to tumor growth or cancer metastasis.

What’s Next?

“This is just the beginning,” Schleiniger noted. “Once we understand the basic rules of cell division, we can begin to ask how they get broken and how to restore order”.This foundational research opens up new directions in cancer biology, regenerative medicine, and computational systems modeling and could pave the way for innovative treatments that go beyond the genetic code, toward the structural logic of life itself.