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

Y Liu, JP Weick, H Liu, R Krencik, X Zhang, L Ma… - Nature …, 2013 - nature.com
Y Liu, JP Weick, H Liu, R Krencik, X Zhang, L Ma, G Zhou, M Ayala, SC Zhang
Nature biotechnology, 2013nature.com
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 …
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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