Article

Medial ganglionic eminence-like cells derived from human embryonic stem cells correct learning and memory deficits.

1] Waisman Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA. [2] Department of Human Anatomy and Histology, Fudan University Shanghai Medical School, Shanghai, China.
Nature Biotechnology (Impact Factor: 39.08). 04/2013; DOI: 10.1038/nbt.2565
Source: PubMed

ABSTRACT Dysfunction of basal forebrain cholinergic neurons (BFCNs) and γ-aminobutyric acid (GABA) interneurons, derived from medial ganglionic eminence (MGE), is implicated in disorders of learning and memory. Here we present a method for differentiating human embryonic stem cells (hESCs) to a nearly uniform population of NKX2.1(+) MGE-like progenitor cells. After transplantation into the hippocampus of mice in which BFCNs and some GABA neurons in the medial septum had been destroyed by mu P75-saporin, human MGE-like progenitors, but not ventral spinal progenitors, produced BFCNs that synaptically connected with endogenous neurons, whereas both progenitors generated similar populations of GABA neurons. Mice transplanted with MGE-like but not spinal progenitors showed improvements in learning and memory deficits. These results suggest that progeny of the MGE-like progenitors, particularly BFCNs, contributed to learning and memory. Our findings support the prospect of using human stem cell-derived MGE-like progenitors in developing therapies for neurological disorders of learning and memory.

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