It’s incredible to contemplate that every human starts from a single founder cell, called the zygote.

From that one founder, specialised cells are formed, building everything from our skin and brain to our blood and bones. Exactly how cells decide what to become – and how they are related – has long been a scientific mystery.

Determining what cells will go on to become is important not just for understanding normal development, but also for identifying when and why things go wrong, leading to disease and disorders.

Lead researcher Professor Shalin Naik said the new technology, which is already being used in numerous labs worldwide, enables scientists to trace the ultimate destiny of cells very early during embryo development.

“When life is a ball of just a few hundred cells, we discovered that some cells could individually give rise to every tissue in the body, while others were already destined to become a certain type of tissue, like brain, gut, limbs or blood” said Prof Naik, a WEHI laboratory head.

“What excites me most is the explosion of research LoxCode enables – it’s not every day you create a tool that’s widely used and has the power to transform what we understand about how our bodies work, at the deepest level.”

Study lead author and LoxCode inventor Dr Tom Weber said the tech is like shuffling and distributing a deck of cards, but at the DNA level.

“With LoxCode each cell is dealt a unique hand which is inherited by its descendants that form the organism. This creates a trackable barcode, allowing us to peer inside this fundamental process with unprecedented detail,” said Dr Weber.

By allowing cells to be traced back to their ancestor cells, LoxCode points to a future where the early roots of developmental disorders can be uncovered.

As part of the study, the research team developed a genetically engineered mouse model that enables cells to be barcoded and analysed through readily available DNA sequencing technology.

LoxCode will be a game changer for biomedical and developmental research, able to generate up to 30 billion random DNA barcodes on demand inside tissues of a live mouse – tens of thousands of times more than existing technologies.

Numerous projects worldwide are currently using the model to investigate a broad range of research questions from brain development and immune cell behaviour, to how organs grow and tissues regenerate after a stroke.

Dr Weber applied his knowledge of physics, synthetic biology and mathematics to optimise the design of the LoxCode sequence, which creates a diversity of over 30 billion barcodes from just 13 small pieces of DNA.

“LoxCode is essentially a DNA ancestry test for every cell, in every tissue of the mouse, that allows researchers to investigate and unravel some of life’s greatest mysteries,” he said.

LoxCode mice are available to order at www.jax.org/strain/037677.

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Header image: Professor Shalin Naik (L) and Dr Tom Weber (R) led a research project that developed LoxCode, a ‘DNA ancestry test for every cell’.