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

Yan Liu, Jason P Weick, Huisheng Liu, Robert Krencik, Xiaoqing Zhang, Lixiang Ma, Guo-min Zhou, Melvin Ayala, Su-Chun Zhang

Research output: Contribution to journalArticle

137 Scopus citations

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 languageEnglish (US)
Pages (from-to)440-7
Number of pages8
JournalNature Biotechnology
Volume31
Issue number5
DOIs
StatePublished - 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

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