Johnson Thomas V, Calkins David J, Fortune Brad, Goldberg Jeffrey L, La Torre Anna, Lamba Deepak A, Meyer Jason S, Reh Thomas A, Wallace Valerie A, Zack Donald J, Baranov Petr
Glaucoma Center of Excellence, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Cellular & Molecular Medicine Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
iScience. 2023 Mar 9;26(4):106361. doi: 10.1016/j.isci.2023.106361. eCollection 2023 Apr 21.
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 mechanisms by which genetically encoded donor cell reporters can be transferred to host neurons through intercellular material transfer. In addition, labeling transplanted 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 regenerative experimental paradigms. Using the retina as an example, we discuss common 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.
通过移植或内源性来源的转分化实现的神经元再填充，在恢复慢性神经退行性疾病或急性损伤中的功能方面具有巨大潜力。评估神经元植入的关键在于从宿主组织内的既有细胞中明确区分出新的或供体神经元。最近的研究已经确定了一些机制，通过这些机制，基因编码的供体细胞报告基因可以通过细胞间物质转移转移到宿主神经元中。此外，在某些情况下，通过病毒载体转导标记移植的和内源性转分化的神经元会在宿主细胞中产生错误表达。这些问题可能会混淆再生实验范式中再填充神经元的追踪和评估。以视网膜为例，我们讨论了用供体细胞报告基因对内源性宿主神经元进行人为标记的常见原因，并提出了一些策略，以防止基于细胞起源错误识别得出错误结论。
