The importance of unambiguous cell origin determination in neuronal repopulation studies

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.

PMID: 37009209
PMCID: PMC10060674
DOI: 10.1016/j.isci.2023.106361

Review

The importance of unambiguous cell origin determination in neuronal repopulation studies

Thomas V Johnson et al. iScience. 2023.

. 2023 Mar 9;26(4):106361.

doi: 10.1016/j.isci.2023.106361. eCollection 2023 Apr 21.

Authors

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.

PMID: 37009209
PMCID: PMC10060674
DOI: 10.1016/j.isci.2023.106361

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

See this image and copyright information in PMC

References

1. MacLaren R.E., Pearson R.A., MacNeil A., Douglas R.H., Salt T.E., Akimoto M., Swaroop A., Sowden J.C., Ali R.R. Retinal repair by transplantation of photoreceptor precursors. Nature. 2006;444:203–207. doi: 10.1038/nature05161. - DOI - PubMed
1. Gonzalez-Cordero A., West E.L., Pearson R.A., Duran Y., Carvalho L.S., Chu C.J., Naeem A., Blackford S.J.I., Georgiadis A., Lakowski J., et al. Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina. Nat. Biotechnol. 2013;31:741–747. doi: 10.1038/nbt.2643. - DOI - PMC - PubMed
1. Barber A.C., Hippert C., Duran Y., West E.L., Bainbridge J.W.B., Warre-Cornish K., Luhmann U.F.O., Lakowski J., Sowden J.C., Ali R.R., Pearson R.A. Repair of the degenerate retina by photoreceptor transplantation. Proc. Natl. Acad. Sci. USA. 2013;110:354–359. doi: 10.1073/pnas.1212677110. - DOI - PMC - PubMed
1. Pearson R.A., Barber A.C., Rizzi M., Hippert C., Xue T., West E.L., Duran Y., Smith A.J., Chuang J.Z., Azam S.A., et al. Restoration of vision after transplantation of photoreceptors. Nature. 2012;485:99–103. doi: 10.1038/nature10997. - DOI - PMC - PubMed
1. Waldron P.V., Di Marco F., Kruczek K., Ribeiro J., Graca A.B., Hippert C., Aghaizu N.D., Kalargyrou A.A., Barber A.C., Grimaldi G., et al. Transplanted donor- or stem cell-derived cone photoreceptors can both integrate and undergo material transfer in an environment-dependent manner. Stem Cell Rep. 2018;10:406–421. doi: 10.1016/j.stemcr.2017.12.008. - DOI - PMC - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

The importance of unambiguous cell origin determination in neuronal repopulation studies

Affiliations

The importance of unambiguous cell origin determination in neuronal repopulation studies

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

Grants and funding

LinkOut - more resources

Full Text Sources