According to new studies from the Massachusetts Institute of Technology (MIT), these ideas have misled researchers for years about the way cell memory works. Historically, researchers conceptualized epigenetic memory as a kind of binary epigenetic switch that would permanently lock genes in an “on” or “off” position. A superb new study from Domitilla Del Vecchio’s lab at MIT provides an inspiring new cell memory picture. Instead, it might work like a dimmer switch, providing more nuanced shades of gene expression rather than just an all-or-nothing response.
Sebastian Palacios, the study’s lead author, published these results in the journal Cell Genomics. These findings indicate that cellular activities are more on a continuum of all the possible activities rather than an on/off switch between completely activated to completely repressed. This exciting finding has the potential to dramatically improve our picture of the complexity of human biology. It will likely show us many more cell types that we haven’t even begun to identify.
The Shift in Understanding Epigenetic Memory
For decades, researchers considered DNA methylation a major player in determining whether or not genes were turned on or off. This concept underlay almost everything they did and knew about genetics.
“Traditionally, scientists have thought that epigenetic memory locks genes either ‘on’ or ‘off’—either fully activated or fully repressed.” – MIT researchers
Del Vecchio and her team decided to test this hypothesis, looking to see how cell changes lasted over a long enough timespan. They monitored the gene expression levels of modified cells for five months, expecting to see them stabilize at either end of the on/off spectrum. Contrary to this binary model, they found inconsistent results.
“We thought this was the dogma. But then we started seeing results that were not consistent with that,” Del Vecchio noted.
What was surprising in the research were the very high proportion of cells that had intermediate expression levels. That means that cells are not binary on/off switches but have the potential to be in many different states.
Implications for Cellular Diversity
By reframing our understanding of cell memory to be more like a dimmer dial, we start to imagine radically different things about cellular diversity. Del Vecchio emphasized that these new targeted techniques are enabling scientists to identify cell types they may have overlooked in the past. They were mostly considering cells with well-established identities.
“It could be that scientists disregarded cells that don’t have a clear commitment, because they assumed this was a transient state,” she explained.
Del Vecchio counters this idea, positing that these so-called intermediate states could be the end game. He continues, they need not be just physical scaffolding.
“But actually these in-between cell types may be permanent states that could have important functions,” she added.
This research is more than just ivory tower academic interest. Its potential to reveal information on heart disease to diabetes, to ALS to asthma, is limitless. The existence of more cell types than previously recognized suggests that there could be undiscovered mechanisms underlying both healthy and diseased states.
Future Directions in Cellular Engineering
As you might imagine, del Vecchio’s group uses a combination of mathematical modeling and genetic engineering to disentangle these dynamic and complex cellular processes. Their original and cutting-edge approach emphasizes the engineering of cells with thrilling new functionalities. This would be an enormous step forward for regenerative medicine and therapeutic strategies more broadly.
Sebastian Palacios gave a compelling argument of epigenetic memory’s role in furthering human complexity.
“One of the things that enables the complexity in humans is epigenetic memory,” he stated.
This study lays the groundwork for continued inquiry into the ways in which cells both establish and uphold their identities. This leads to fundamental queries about the expression of genes. How does its subcellular distribution determine the cellular communication with neighbors, cell fate during development and adaptation to environmental changes?
Researchers have begun to fully explore the field of epigenetics. They are on the verge of discovering even more about the potential of cellular reprogramming and providing groundbreaking treatments for all sorts of diseases and disorders.