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

1] Waisman Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA. [2] Department of Human Anatomy and Histology, Fudan University Shanghai Medical School, Shanghai, China.
Nature Biotechnology (Impact Factor: 41.51). 04/2013; DOI: 10.1038/nbt.2565
Source: PubMed


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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Available from: Huisheng Liu, Sep 09, 2014
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    • "In a related study, this group reported the use of this method to successfully direct the differentiation of hESCs to medial ganglionic eminence progenitors and subsequently, GABA interneurons (Liu et al., 2013b). Interestingly, the transplantation of hESC-derived medial ganglionic eminence progenitors to the hippocampi of mice led to behavioural changes in learning and memory (Liu et al., 2013b). These findings show that in addition to the study of basic neurobiology, hiPSCs and hESCs can be also used to investigate behaviours associated with specific neuronal subtypes. "
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    • "Human neurons were differentiated from iPSCs as previously described (Gamm et al., 2008; Hu and Zhang, 2009; Liu et al., 2013; Pankratz et al., 2007). Neurospheres were plated onto glass coverslips coated with poly-Dlysine (PDL) and laminin (PDL-LN) and cultured in neural basal media with B27 supplements (Gibco). "
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    • "Under optimal conditions, over 90% of the cells express NKX 2.1, thereby demonstrates MGE identity. These neurons are 45% cholinergic and 55% GABAergic (Liu et al., 2013b). This underlines the general fact that in vitro patterning can indeed specify the regional identity of cells in a highly effective manner, however, full specification to a single cell type (e.g., solely cholinergic) cannot be achieved in this way. "
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