The importance of unambiguous cell origin determination in neuronal repopulation studies

Neuronal repopulation achieved through transplantation or transdifferentiation from endogenous sources holds tremendous potential for restoring function in chronic neurodegenerative disease or acute injury. Key to the evaluation of neuronal engraftment is the definitive discrimination of new or donor neurons from preexisting cells within the host tissue. Recent work has identified mecha-nisms by which genetically encoded donor cell reporters can be transferred to host neurons through intercellular material transfer. In addition, labeling trans-planted and endogenously transdifferentiated neurons through viral vector transduction can yield misexpression in host cells in some circumstances. These issues can confound the tracking and evaluation of repopulated neurons in regen-erative experimental paradigms. Using the retina as an example, we discuss com-mon reasons for artifactual labeling of endogenous host neurons with donor cell reporters and suggest strategies to prevent erroneous conclusions based on misidentification of cell origin.

Automated summary

Neuronal repopulation, achieved through transplantation or transdifferentiation, has the potential to restore function in neurodegenerative diseases or acute injuries. The evaluation of engrafted neurons is crucial and recent studies have identified mechanisms for cell reporter transfer and misexpression in host cells, leading to potential misidentification of cell origin. This article discusses the common reasons for artifactual labeling of host neurons with donor cell reporters, using the retina as an example, and suggests strategies to prevent erroneous conclusions based on misidentification of cell origin.