Umeå University discovers critical mechanisms in stem cell differentiation

A study led by Umeå University, Sweden, presents new discoveries about how stem cells develop and transition into specialised cells. The discovery can provide increased understanding of how cells divide and grow uncontrollably so that cancer develops.

The discovery opens a new track for future research into developing new and more effective treatments for certain cancers."

Francesca Aguilo, Department of Molecular Biology, Umeå University

All cells in the body arise from a single fertilized egg. From this single origin, various specialized cells with widely differing tasks evolve through a process called cellular differentiation. Although all cells share the same origin and share the same genetic information, specialized cells use the information in different ways to perform different functions. This process is regulated by genetic and epigenetic mechanisms.

In the current study, researchers have studied embryonic stem cells from mice to understand how the cells transition from a versatile state to become specialized cells. A key player in this process is the protein LSD1. It is overexpressed in many cancers and is therefore an important goal in cancer treatment research. Several clinical trials are testing to inhibit the LSD1 protein's ability to modify gene expression.

However, the study shows that LSD1 not only affects gene expression in the way previously assumed by altering histones, i.e. proteins around which the long DNA helixes of chromosomes are coiled, but LSD1 also acts as a scaffold, a support structure for other proteins that control DNA methylation. The researchers were able to see that even when LSD1's enzymatic function was inhibited, its support ability could still maintain DNA methylation patterns necessary for cell differentiation and proliferation. Abnormal DNA methylation is strongly associated with cancer.

The results suggest that, for cancer treatments to be effective, it may not be enough to simply target blocking LSD1's enzymatic activity. Treatments may also need to focus on also attacking LSD1's supporting role.
"So far, this is basic research, so there is a long way to go and it is too early to make any promises about new treatments, but it could be an important step for continued cancer research," says Francesca Aguilo.

The study has been led from Umeå University in collaboration with various institutions including the University of Pavia, University of Texas Health Science Center at Houston, Universidad de Extremadura, and others. It is published in the scientific journal Nature Communications.

The study is funded by the Swedish Research Council, the Swedish Cancer Society, the Knut and Alice Wallenberg Foundation and the Kempe Foundations.