The in vivo timeline of differentiation of engrafted human neural progenitor cells

Understanding the individual timeline of stem cell differentiation in vivo is critical for evaluating stem cell properties in animal models. However, with conventional ex vivo techniques, such as histology, the individual timeline of differentiation is not accessible. Therefore, we designed lentivir...

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Bibliographic Details
Published in:Stem cell research 2019-05, Vol.37, p.101429-101429, Article 101429
Main Authors: Vogel, Stefanie, Schäfer, Cordula, Hess, Simon, Folz-Donahue, Kat, Nelles, Melanie, Minassian, Anuka, Schwarz, Martin K., Kukat, Christian, Ehrlich, Marc, Zaehres, Holm, Kloppenburg, Peter, Hoehn, Mathias, Aswendt, Markus
Format: Article
Language:English
Subjects:
Animals
Astrocytes - cytology
Bioluminescence imaging
Cell Differentiation
Cell Lineage
Cells, Cultured
Cerebral cortex
Humans
In vivo brain imaging
Induced Pluripotent Stem Cells - cytology
Male
Mice
Neural Stem Cells - cytology
Neurogenesis
Neurons - cytology
Nude mice
Oligodendroglia - cytology
Stem cell differentiation
Stem cell implantation
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Summary:Understanding the individual timeline of stem cell differentiation in vivo is critical for evaluating stem cell properties in animal models. However, with conventional ex vivo techniques, such as histology, the individual timeline of differentiation is not accessible. Therefore, we designed lentiviral plasmids with cell-specific promoters to control the expression of bioluminescence and fluorescence imaging reporters. Promoter-dependent reporter expression in transduced human induced pluripotent stem cell-derived neural progenitor cells (hNPCs) was an effective indicator of differentiation in cell culture. A 12-week in vivo imaging observation period revealed the time profile of differentiation of engrafted hNPCs in the mouse brain into astrocytes and mature neurons which was verified by immunostainings, patch-clamp electrophysiology, and light-sheet fluorescence microscopy. The lentiviral vectors validated in this study provide an efficient imaging toolbox for non-invasive and longitudinal characterization of stem cell differentiation, in vitro screenings, and in vivo studies of cell therapy in animal models. •Cell-specific imaging of stem cell differentiation using lentiviral plasmids.•Imaging reporters engineered for DCX, MAP2, eSyn, GAD67, GFAP or PLP expression.•Differentiation of hNPCs into neurons, astrocytes and oligodendrocytes in vitro.•Spontaneous differentiation of grafted hNPCs in mouse cortex imaged for 12 weeks.•A subset matures to action-potential generating neurons with neuronal morphology.
ISSN:1873-5061
1876-7753
DOI:10.1016/j.scr.2019.101429