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Human Neural Progenitor Cells Incorporate into Functional Network in Mouse Hippocampus

Jiani Hong, Liuqing Yang
World Scientific Research Journal, (2026), Vol.12, No.6, pp.10-18
Published: June 16, 2026
DOI: 10.6911/WSRJ.202606_12(6).0002
PDF: Download Full Text PDF
Abstract

Human neural progenitor cell (NPC) transplantation into mouse brain has been widely used as an in vivo human-relevant model system. The integration of differentiated human cells or tissue with local circuit has also been intensively investigated. However, as part of the central nervous system which governs the behaviors of living organisms, evidence on whether xenografted neurons are responsive to mouse behavior in intended ways is still poor. In this work, we transplanted iPSC-derived NPCs (iNPCs) into the hilus region of mouse hippocampus and monitored their survival, migration, differentiation and integration in different host mouse lines for different timespan. We found that iNPCs survived for up to two months in C57BL6 mice and for more than six months in Rag2 KO immunodeficient mice. To assess functional integration, we performed contextual fear conditioning with Rag2 KO xenograft mice and examined endogenous Fos protein expression. Dentate gyrus neurons are largely silent and sparsely activated during contextual information learning. We found that fear conditioning training induces Fos gene expression in iNPC-differentiated neurons 6 months after transplantation. The result suggests that behavior-responsive functional integration of human xenografted neurons in mouse hippocampus can be formed after long-time integration.

Keywords: iNPCs; hippocampus xenotransplantation; functional integration.
APA Citation: Jiani Hong, Liuqing Yang (2026). Human Neural Progenitor Cells Incorporate into Functional Network in Mouse Hippocampus. World Scientific Research Journal, 12(6), 10-18. https://doi.org/10.6911/WSRJ.202606_12(6).0002

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