ESC-derived basal forebrain cholinergic neurons ameliorate the cognitive symptoms associated with Alzheimer's disease in mouse models

Wei Yue, Yuanyuan Li, Ting Zhang, Man Jiang, Yun Qian, Min Zhang, Nengyin Sheng, Su Feng, Ke Tang, Xiang Yu, Yousheng Shu, Chunmei Yue*, Naihe Jing

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)

Abstract

Degeneration of basal forebrain cholinergic neurons (BFCNs) is associated with cognitive impairments of Alzheimer's disease (AD), implying that BFCNs hold potentials in exploring stem cell-based replacement therapy for AD. However, studies on derivation of BFCNs from embryonic stem cells (ESCs) are limited, and the application of ESC-derived BFCNs remains to be determined. Here, we report on differentiation approaches for directing both mouse and human ESCs into mature BFCNs. These ESC-derived BFCNs exhibit features similar to those of their in vivo counterparts and acquire appropriate functional properties. After transplantation into the basal forebrain of AD model mice, ESC-derived BFCN progenitors predominantly differentiate into mature cholinergic neurons that functionally integrate into the endogenous basal forebrain cholinergic projection system. The AD mice grafted with mouse or human BFCNs exhibit improvements in learning and memory performances. Our findings suggest a promising perspective of ESC-derived BFCNs in the development of stem cell-based therapies for treatment of AD.

Original languageEnglish
Pages (from-to)776-790
Number of pages15
JournalStem Cell Reports
Volume5
Issue number5
DOIs
Publication statusPublished - 10 Nov 2015
Externally publishedYes

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