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

Nat Biotechnol. 2013 May;31(5):440-7. doi: 10.1038/nbt.2565. Epub 2013 Apr 21.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Hippocampus / surgery*
  • Humans
  • Interneurons / metabolism*
  • Interneurons / pathology*
  • Learning Disabilities / metabolism
  • Learning Disabilities / pathology
  • Learning Disabilities / surgery
  • Memory Disorders / diagnosis
  • Memory Disorders / physiopathology*
  • Memory Disorders / surgery*
  • Mice
  • Stem Cell Transplantation / methods*
  • Treatment Outcome