title: Medial ganglionic eminence-like cells derived from human embryonic stem cells correct learning and memory deficits.
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.
authors.affiliation: Waisman Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Jason P
authors.initials: JP
authors.lastname: Weick
authors.forename: Huisheng
authors.initials: H
authors.lastname: Liu
authors.forename: Robert
authors.initials: R
authors.lastname: Krencik
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Lixiang
authors.initials: L
authors.lastname: Ma
authors.forename: Guo-min
authors.initials: GM
authors.lastname: Zhou
authors.forename: Melvin
authors.initials: M
authors.lastname: Ayala
authors.forename: Su-Chun
authors.initials: SC
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D006801:Humans; D007395:Interneurons / Q000378:metabolism* / Q000473:pathology*; D007859:Learning Disabilities / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008569:Memory Disorders / Q000175:diagnosis / Q000503:physiopathology* / Q000601:surgery*; D051379:Mice; D033581:Stem Cell Transplantation / Q000379:methods*; D016896:Treatment Outcome