Yale Researchers Create ‘Ancestry.com’ for Cells

A new study reveals an innovative method for tracking a cell’s lineage all the way back to its original embryonic parent cell.

(CN) — Scientists have developed a new state of the art technique to view a cell’s entire life story, allowing them to trace a single skin cell’s lineage from its earliest stage in embryonic development to its full maturity at adulthood.

In a study published Thursday in the journal Science, a team of researchers from Yale University and the Mayo Clinic discuss their new technique and its implications in the field of cellular biology.

Cellular lineage describes where a cell came from and what occurred to change it into one of the trillions of cells in the human body with a specific job to do. Some experts view cell lineage as one of the most important aspects of developmental biology as it provides scientists with an in-depth understanding of an organism’s genetics and overall health.

As cells begin developing in the embryonic stage, they develop variations over time, splitting up into different groups of cells each with their own function in the body. These are called somatic mutations, which refers to a variation in a cell that is gained and not inherited. The more a cell continues to divide and mutate, the less recognizable it is from the cell it originated from, which is where the study of cell lineage comes in.

To discern the origins of a cell, scientists must retrace the steps of its mutations to find the source, like a biological treasure hunt. The authors explain that if numerous cells are high in traces of a mutation, it’s probable that the mutation occurred early in the cells’ development — making them closer in resemblance to the parent cell they came from.

“It’s like Ancestry.com for our bodies,” said co-senior author Flora Vaccarino, neuroscience professor and Harris Professor in the Yale Child Study Center.

Vaccarino and her colleagues decided to look specifically at skin cells for their research due to the fact that some of their mutations can occur very early in embryonic development, which is proven by their presence in adult blood, saliva, and urine. Since the mutation can occur in each of these fluids, which are constantly being expelled and replicated, it stands to reason that the mutation is being copied from a very old original cell that goes back all the way to early embryonic development. 

This is further explained when the process of embryonic development is taken into account. An embryo starts out as one germ cell, and over time it builds into different germ layers, each of which eventually become the connecting tissue, nervous system, blood, and more. If cells in the early stages of this development undergo mutations, it’s as if the mutation is then being copied and pasted into the new cells as they divide and multiply, and the mutations are carried across these layers.

For their experiment, the researchers obtained the skin cells they needed from two human participants. They then analyzed the genomes of those cells and identified their various genetic mutations, allowing them to follow the clues and track the cells’ lineage. They found that the mutations were in fact passed down from cell to cell as the body grew from its earliest stages into maturity, which paved the way for the team to accurately document cellular lineage.

“Cellular history has consequences,” Vaccarino said.

These findings provide a promising future in the study of developmental disabilities, as scientists may be able to use their technique to track down the sources of them. The authors offer schizophrenia and autism as prime examples, both commonly misunderstood disorders characterized by abnormalities in the brain. They occur because of a cellular mutation that takes place very early and throws regular development off course, affecting the rest of the growth process. The hope is that eventually, that mutation could be traced back to the very cell it originated from, and experts can gain a deeper understanding of the cause.

Another interesting find was how cell lineages don’t often get distributed equally at the first division. The authors found that upon division, one of the cells could contribute to making up 90% of the human body while the other cell could focus only on creating the placenta, for example.

While this cutting-edge research is a significant step forward, Vaccarino adds that technology tracking cellular lineage through embryonic development remains out of reach and will require more studies.

“We have figured out a minimally invasive way to peer into a window of a person’s personal cellular history,” she said.

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