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Research ArticleFeature: Research Highlights, Development

Transplanted Human Induced Pluripotent Stem Cell-Derived Neurons Wire and Fire with Balanced Excitation–Inhibition in Rat Cortex

Rosalind S.E. Carney [DPhil]
eNeuro 16 April 2020, 7 (2) ENEURO.0041-20.2020; DOI: https://doi.org/10.1523/ENEURO.0041-20.2020
Rosalind S.E. Carney
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    Figure 1.

    Generation and transplantation of forebrain progenitors from hiPSCs. In culture, human ESCs and induced pluripotent cells (hES/iPS) developed into embryoid bodies (EB; day 7), RONAs (day 15), neurospheres (day 29), and hNPCs (day 30). Thereafter, hNPCs were transplanted into neonatal rat cortex or maintained in vitro. Ten weeks after transplantation, the fate of xenotransplanted and cultured cells were compared. (Adapted from Figure 1 in Yin et al., 2019.)

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    Figure 2.

    hiPSC-derived neurons integrate into the rat brain. A, Representative hippocampal brain slice showing RFP+ cells (red) and nuclear DAPI stain (blue). B–D, High-power images of the dentate gyrus (DG) from the boxed area in A showing RFP-labeled cells (B), immunoreactivity for the mature neuronal marker MAP2 (C; green), and the merged image of A, C (D). CA, cornu ammonis; scale bar, 100 μm. (Adapted from Figure 4 in Yin et al., 2019.)

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    Figure 3.

    hiPSC-derived neurons functionally integrate into the synaptic circuitry of the rat brain 10 weeks after transplantation. A, AP firing patterns of hiPSC-derived neurons. Increased AP firing was observed with increasing current injection. B, Representative traces of whole-cell Na+ (inward) and K+ (outward) currents recorded from grafted cells, elicited by voltage steps from −100 to +60 mV in 20-mV increments, and blocked by TTX and TEA, respectively. C, D, I–V curves for voltage-gated Na+ (C) and K+ (D) currents. E, Representative traces of sEPSCs and sIPSCs recorded in voltage-clamp configuration at −70 mV. sEPSCs were obtained in the presence of picrotoxin (100 μM), and sIPSCs were recorded in the presence of CNQX (20 μM) and d-AP5 (50 Mm). F, AMPA receptor-mediated postsynaptic currents were evoked by stimulation delivered from an electrode placed ∼200–300 μm away from the transplanted cell, which was blocked by the subsequent application of CNQX. (Adapted from Figure 5 in Yin et al., 2019.)

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eneuro: 7 (2)
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Vol. 7, Issue 2
March/April 2020
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Transplanted Human Induced Pluripotent Stem Cell-Derived Neurons Wire and Fire with Balanced Excitation–Inhibition in Rat Cortex
Rosalind S.E. Carney
eNeuro 16 April 2020, 7 (2) ENEURO.0041-20.2020; DOI: 10.1523/ENEURO.0041-20.2020

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Transplanted Human Induced Pluripotent Stem Cell-Derived Neurons Wire and Fire with Balanced Excitation–Inhibition in Rat Cortex
Rosalind S.E. Carney
eNeuro 16 April 2020, 7 (2) ENEURO.0041-20.2020; DOI: 10.1523/ENEURO.0041-20.2020
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