A new paper published in Cell Stem Cell by researchers from Mount Sinai reports that one specific protein controls the functions of stem cells that make them more useful in terms of usage in regenerative medicine.
Most living organisms, including humans, start from an unspecialized single cell, later on multiplying and differentiating to multiple cells types which have specific functions. In humans, these undifferentiated cells are called stem cells, and they multiply and differentiate in the womb of the pregnant mother to become all types of cells in the body. In order for stem cells to be safely used in medical treatment, many factors have to be controlled. These include cell pluripotency, cell differentiation ability, and self-renewal or immortality (which is the ability to multiply ideally indefinitely).
The Wonders of Stem Cells
Stem cells must be able to exhibit self-renewal because they usually have to be kept until they are used as replacements for specific cell types, which is basically the core of regenerative medicine. On the other hand, the ability of self-renewal should not also go out of hand, as uncontrolled proliferation of these cells could also possibly cause abnormal tissue growth as seen in tumors and cancers.
According to the study published by the Mount Sinai researchers, with the use of mouse embryonic stem cells, a protein called ZFP217 (zinc finger protein 217), was found to have the ability to regulate the functionality of genes that are involved in the balance between stem cell self-renewal and differentiation.
Lead author Dr. Martin Walsh says that they are hoping that ZFP217 could be used to maintain supplies of therapeutic stem cells. ZFP217 is also associated with poor survival in a variety of cancer types, and further studying how this protein functions would possibly make way to discover methods in predicting cancer risk, earlier diagnosis, and providing novel therapeutic methods.
In the study, ZFP217 was found to regulate N6-Methyladenosine (m6A), which is the most commonly occurring RNA modification in human cells that consequently affects stability and genetic function. ZFP217 regulates m6A deposition on mRNAs produced by stem cell pluripotency genes by attaching it to another enzyme called m6A methyltransferase-like 3 (METTL3), causing it to become inactive. This process causes the cells to differentiate, and ending their self-renewal ability.
Results of the study also show that ZFP217 is involved in cancer proliferation. Overexpression of this gene allows tumor cells to proliferate indefinitely and also blocking pathways that cause cells to mature into functional types.
Other results revealed that ZFP217 also activates genes such as Nanog and Sox2, which are involved in the cells' stemness. Factors such as these may also in turn influence ZFP217, akin to the feedback loop mostly seen in genetic regulation.
Ever since 2006, many researchers around the world have been able to take many kinds of differentiated cells, such as skin cells, and by using genetic techniques, transform them into induced pluripotent stem cells or iPSCs. As the original mature cells came from one patient, the transformed iPSCs will also be specific to that patient. This offers a good option for personalized treatment in the form of stem cells. Nanog and Sox2 are actually two of the factors being used in transforming mature cells into iPSCs, and the close ties of these two enzymes to ZFP217 could possibly mean that ZFP217 is a new tool that can be used to make more effective production of iPSCs.
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Written by: Yevgeny Aster Dulla, MSc