Yale scientists have found that stress responses to starvation — an experience a yeast cell might endure — can be inherited by progeny.
When deprived of glucose — their food source — yeast cells respond by activating proteins called transcription factors. These proteins move to the cells’ nuclei and cause a variety of different genes to be expressed. By tracking single cells, the researchers found that if a parent cell was placed under glucose-limitation stress, its daughter cells would be on average more prepared to handle glucose-starvation. These changes are epigenetic, meaning they alter the expression of genes without necessarily altering the underlying genetic code. The results of the study were published on April 18 in the journal Science Advances.
“Daughter cells are able to inherit the [stress] response of their mother cells, and this epigenetic inheritance was observed at the single-cell level,” said Meenakshi Chatterjee GRD ’17, first author of the study. “Understanding these variations can have medical consequences, and potentially be very important to understanding the sensitivity of cells to different drug types.”
A study of how characteristics are passed from mother to daughter cell epigenetically has the potential to foster a broader understanding of variation among cells, Chatterjee said.
When yeast cells are stressed in low-glucose environments, a transcription factor protein named Msn2 moves to the nucleus from the cytoplasm and activates the expression of many downstream genes, said senior author Murat Acar, a physics and molecular, cellular and developmental biology professor at West Campus’ Systems Biology Institute.
The researchers wanted to measure the precise dynamics of Msn2’s journey to the nucleus under different stress levels, Acar continued.
Often, Chatterjee said, biologists study cells on a population level by taking averages as opposed to tracking individual cells. But in recent years, she continued, scientists have focused more on studying cells at the individual level in order not to miss valuable information that might otherwise get overlooked.
In order to follow individual cells, the team first had to create an experimental tool to follow single cells as they reproduce. They came up with a microfluidic device that could track not only a cell, but its daughter and granddaughter cells as well. Then they deprived the parent cells of glucose and observed those cells’ stress responses, as well as the daughter and granddaughter cells. Later, they used imaging techniques to conduct further analyses.
When scientists study cells solely on the population level, the impacts of familial relations between cells are “washed out” in the analysis, Chatterjee said.
“The value of a single cell [approach], what properties it has, and how it responds to certain stress, have not been studied as much as we would like.” Chatterjee said. “The novel part of this is that you would treat every cell as a unique individual and look at its stress response, and then do that for every cell, and you could start to see the trend emerging from familial relationships.”
Maya Chandra | maya.chandra@yale.edu