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bioRxiv · 10.1101/2025.03.31.646380

Characterization of the intraspecies chimeric mouse brain at embryonic day 12.5

Strell, P.·Waldron, M. A.·Johnson, S.·Shetty, A. V.·Crane, A.·Steer, C.·Low, W. C.
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Abstract

Incidence of neurodegenerative diseases such as Alzheimers, Parkinsons, Huntingtons, and amyotrophic lateral sclerosis have increased dramatically as life expectancy at birth has risen year-over-year and the population ages. Neurological changes within the central nervous system, specifically the brain, include cell loss and deterioration that impact motor function, memory, executive function, and mood. Available treatments are limited and often only address symptomatic manifestations of the disease rather than disease progression. Cell transplantation therapy has shown promise for treating neurodegenerative diseases, but a source of autologous cells is required. Blastocyst complementation provides an innovative method for generating those autologous neural cells. By injecting mouse induced pluripotent stem cells (iPSCs) into a wild type (WT) mouse blastocyst, we generated a chimeric mouse brain derived of both donor and host neuronal and non-neuronal cells. An embryonic day 12.5 (E12.5), automated image analysis of mouse-mouse chimeric brains showed the presence of GFP-labeled donor-derived dopaminergic and serotonergic neuronal precursors. GFP-labeled donor-derived cholinergic precursor neurons and non-neuronal microglia-like and macrophage-like cells were also observed using more conventional imaging analysis software. This work demonstrates that the generation of mouse-mouse chimeric neural cells is possible; and that characterization of early neuronal and non-neuronal precursors provides a first step towards utilizing these cells for cell transplantation therapies for neurodegenerative diseases.

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Strell, P., Waldron, M. A., Johnson, S., Shetty, A. V., Crane, A., Steer, C., Low, W. C.. 2025-04-02. Characterization of the intraspecies chimeric mouse brain at embryonic day 12.5. https://doi.org/10.1101/2025.03.31.646380

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