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Inside the Stem Cell Differentiation Process

Jesse Jenkins

New evidence shows that stem cells can distinguish between sister chromosomes with different epigenetic modifications during cell division. Learn more...

In the beginning, we are all just a single cell. That cell divides and differentiates, producing daughter cells with the same genome but different sizes, shapes, and functions. However, exactly how cells differentiate into such a wide variety of cell types remains unclear.

By tagging copies of Y chromosomes with either red or blue, researchers have found that cells can distinguish between two copies of the same chromosome during stem cell division. Source: Yukiko Yamashita

Now researchers at the University of Michigan have found for the first time that cells can distinguish between two copies of the same chromosome, which are identical in terms of DNA sequence but not in epigenetic content, during stem cell division. These findings suggest that epigenetic information in the form of DNA or chromatin modifications is transmitted non-randomly on chromosome copies to daughter cells, dictating cell fate.

"Before the cells adopt their fates, they already inherited genomes with the right epigenetic information that allows the cells to adopt their fates,” said Yukiko Yamashita, a MacAurthur Fellow and assistant professor of cell and developmental biology at the University of Michigan Medical School and author of a paper published in Nature this week (1).

To find evidence for this selective inheritance, Yamashita and her lab looked at the germline stem cells of male Drosophila flies, which are relatively large in size, allowing for single-cell resolution. “The single cell resolution with 100% accuracy really distinguishes this system from others where you actually have to handle all stem cells as a bulk,” explained Yamashita.

When Drosophila germline stem cells divide, they produce two new cells: another germline cell or a gonialblast that later develops into a sperm cell. So Yamashita and colleagues wanted to analyze how the copies of each chromosome were separated into those cells.

To do so, Yamashita’s team used chromosome orientation fluorescence in situ hybridization (CO-FISH). Unlike standard FISH, this method allowed the researchers to tag individual strands of the target DNA so that they could monitor each copy of chromosomal DNA in the germline stem cells during cell division.

In the end, the team found that copies of X and Y chromosomes were being separated in a non-random pattern that ultimately determined the daughter cell’s fate as either a germline cell or a gonialblast. This pattern was not evident for other chromosomes, suggesting that the cells distinguish between chromosomes with different epigenetic content.

Now, Yamashita and colleagues hope to conduct further tests to better define the molecular mechanisms involved and determine which molecules responsible for the process. Yamashita believes that this knowledge will lead to a better understanding of the process’ biological significance as well.

“Once you clearly understand how cells are making this happen, that will probably illuminate why this is happening too…but those are two directions that are intertwined,” said Yamashita.


1. Yadlapalli, S., and Y. M. Yamashita. 2013. Chromosome-specific nonrandom sister chromatid segregation during stem-cell division. Nature advance online publication(May).

Keywords:  stem cells