The importance of unambiguous cell origin determination in neuronal repopulation studies

Thomas V Johnson; David J Calkins; Brad Fortune; Jeffrey L Goldberg; Anna La Torre; Deepak A Lamba; Jason S Meyer; Thomas A Reh; Valerie A Wallace; Donald J Zack; Petr Baranov

doi:10.1016/j.isci.2023.106361

The importance of unambiguous cell origin determination in neuronal repopulation studies

iScience. 2023 Mar 9;26(4):106361. doi: 10.1016/j.isci.2023.106361. eCollection 2023 Apr 21.

Authors

Thomas V Johnson^{1

2}, David J Calkins³, Brad Fortune⁴, Jeffrey L Goldberg⁵, Anna La Torre⁶, Deepak A Lamba⁷, Jason S Meyer⁸, Thomas A Reh⁹, Valerie A Wallace¹⁰, Donald J Zack^{1

11}, Petr Baranov¹²

Affiliations

¹ Glaucoma Center of Excellence, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Cellular & Molecular Medicine Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ The Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
⁴ Discoveries in Sight Research Laboratories, Devers Eye Institute and Legacy Research Institute, Legacy Healthy, Portland, OR, USA.
⁵ Spencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, USA.
⁶ Department of Cell Biology & Human Anatomy, University of California Davis, Davis, CA, USA.
⁷ Department of Ophthalmology and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
⁸ Departments of Medical & Molecular Genetics, Ophthalmology (Glick Eye Institute), Pharmacology & Toxicology, and Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
⁹ Department of Biological Structure, University of Washington, Seattle, WA, USA.
¹⁰ Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Departments of Laboratory Medicine & Pathobiology, and Ophthalmology & Vision Sciences, University of Toronto, Toronto, ON, Canada.
¹¹ Departments of Neuroscience, Molecular Biology & Genetics, and Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹² Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.

Abstract

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.

Keywords: Cell biology; Molecular biology; Neuroscience.

Publication types

Review

Abstract

Publication types

Grants and funding