Dr. Jacques Drouin and his team, at the IRCM Molecular Genetics Research Unit, recently published a very interesting review taking stock of recent scientific knowledge on important underlying mechanisms of cell differentiation, their role in pathogenesis as well as their therapeutic potential. The review graced the front page of the July edition of the prestigious Nature Review Molecular Cell Biology journal, which testifies to its scientific importance.
A Possible Therapeutic Avenue
Many deformities, developmental defects or pathologies such as cancers, have their origins during the cell differentiation process. The good news is that Drouin’s team has been shedding light on an avenue that could well be the foundation of future epigenetic therapies.
Cell differentiation is the process by which living organisms develop from the fertilized egg into multicellular organisms. This process requires complex DNA decoding mechanisms, for cells to differentiate sequentially, leading to the creation of different tissues and organs that make up a functioning body. In mammals, no need to say how instrumental cell differentiation is for proper development and function, and consequently, for good health.
" For years, our lab has thrived to understand how genes work and how their disruption causes disease," said Dr. Jacques Drouin.
Pioneer Factors Are the Key Holder
During the cell differentiation process, transcription factors are regulators that decide which DNA to decode. Among them, only a very small subset has the unique ability to trigger the opening of so-called closed DNA domains and thus allow the expression of underlying genes: they are called Pioneer factors.
“It is as if entire sections of the genome are zipped away, and pioneer factors hold the key to unzip them and retrieve genetic information that is essential for cells to know how to develop and what to do,” explained Dr. Drouin
Years ago, Drouin’s team discovered a pioneer factor, and how unlike other transcription factors, pioneers are master regulators of development and cell differentiation. Recent investigations have also demonstrated pioneer factors’ power, as promising tools for cellular reprogramming and novel cell therapies.
Pioneer factors act upstream of a regulatory cascade that jointly defines each cell’s identity and function. Pioneer factors are therefore critical for all attempts at cellular reprogramming that aim to create useful cells in a perspective of cellular transplants/replacements, which could help treat diseases such as diabetes or Parkinson's disease.
However, with this unique regulatory power of pioneer factors also comes with the possibility of errors, which translate into developmental defects or even cancer.
Understanding the action of pioneers is therefore critical to understand the pathogenic mechanisms of cancer and to use this knowledge for new therapeutic approaches.
Congratulations to Dr. Drouin and his collaborators for this important work.
