Key gene-regulating protein observed to control stem cell properties that could improve their utility in regenerative medicine
Researchers from Mount Sinai (NY, USA) have observed the zinc finger protein ZFP217 to regulate the actions of genes responsible for maintaining a balance between stem cell self-renewal and differentiation.
This study was carried out in mouse embryonic stem cells, considered good cell models for studying processes seen in human stem cells. In the investigation, ZFP217 was found to regulate N6-methyladenosine (m6A) deposition onto mRNAs created by stem cell pluripotency genes through attachment to the METTL3 enzyme and rendering it inactive. This action prevents methylations that would otherwise cause the stem cells to differentiate, causing them to lose their self-renewal and pluripotency.
These findings also provide further argument for the hypothesis that m6A methylation, partly controlled by ZPF217 signaling, is relevant in human cancers. ZNF217 overexpression is known to provide an advantage to tumor cells by allowing them to infinitely proliferate and downregulating pathways that typically instruct cells to mature into function cells.
The investigators also discovered that ZFP217 turns on the genes important for stemness, including Nanog and Sox2. Human ZFP217 may in turn also be influenced by these same factors, in a feedback loop similar to that seen in complex genetic regulation.
Lead study author Martin Walsh (Icahn School of Medicine, Mount Sinai) explained the potential impact of this working, stating: “The hope is that ZPF217 could be used to maintain supplies of therapeutic stem cells. At the same time, as the human ZNF217 is associated with poor survival in a variety of cancers, understanding how this protein operates in physiological conditions may help to predict cancer risk, achieve earlier diagnosis and provide novel therapeutic approaches.”
— Written by Hannah Wilson