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.
Original language | English (US) |
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Pages (from-to) | 440-7 |
Number of pages | 8 |
Journal | Nature Biotechnology |
Volume | 31 |
Issue number | 5 |
DOIs | |
State | Published - May 2013 |
Keywords
- Animals
- Cell Differentiation
- Cells, Cultured
- Hippocampus
- Humans
- Interneurons
- Learning Disorders
- Memory Disorders
- Mice
- Stem Cell Transplantation
- Treatment Outcome
- Journal Article
- Research Support, N.I.H., Extramural