Researchers at NYU Abu Dhabi (NYUAD) have discovered the code that is associated with the liver’s genome (complete set of DNA) and its ability to regenerate.
According to a recent article in MedicalXpress, the NYUAD team reasoned that the genes responsible for the regeneration of the liver must be activated by the same code that causes their response when tissues or organ parts are cut out.
These findings establish entirely new insights into the way in which certain genes can be activated when a part of the liver is taken out.
The Discovery
Currently, the norm for humans and other mammals to regenerate their liver occurs only when a portion of the liver is intentionally removed or as a result of an injury.
Genes that are involved in liver cell growth are silent in non-regenerating livers. Therefore, the researchers were surprised to learn that the genes were located in areas of the genome that housed the most active genes.
The NYUAD team, led by Dr. Kirsten Sadler Edepli, used a laboratory mouse model for the study as the mouse model contains elements of the epigenetic code that cause the activation of pro-regenerative genes when signaled.
The researchers focused on the epigenome which involves chemical modifications to the DNA rather than specifically changing the genetic code.
The epigenetic code (tissue-specific) consists of protein complexes that can identify histone modifications. Note that histone modification is involved in creating patterns of gene repression.
H3K27me3 modification
A second revelation came when the team found that pro-regenerative genes were marked with the H3K27me3 modification.
The timing of the removal or addition of H3K27me3 enables differentiation throughout every stage of tumor development. Differentiation is defined as the level to which tumor cells mimic their cell of origin. Tumors that resemble their cell of origin translates to treatment evasion and poor prognosis.
Examining the mouse liver, the team identified six chromatin states that correlated to epigenetic marks. They created the first-ever chromatin map of the liver depicting elements that are necessary for the liver’s regeneration. Chromatin is defined as matter within a cell nucleus consisting of RNA, DNA, and proteins. During cell division, chromatin forms chromosomes.
Looking Forward
The NYUAD finding has identified a mechanism that maintains liver cells as ready to be activated and regenerate.
Beyond that, the new findings could bring about a new type of medicine that would enable organs that are currently non-regenerative to regrow.
Dr. Sadler explains that the ability to regenerate, which declines as people age, is hidden in the epigenome of the liver. The team is continuing the study of the code and its promise of expanding regenerative medicine.
