@article{a5d20adb482141ff855f67e36b21aa5e,
title = "Neurons derived from human induced pluripotent stem cells integrate into rat brain circuits and maintain both excitatory and inhibitory synaptic activities",
abstract = "The human cerebral cortex is a complex structure with tightly interconnected excitatory and inhibitory neuronal networks. In order to study human cortical function, we recently developed a method to generate cortical neurons from human induced pluripotent stem cells (hiPSCs) that form both excitatory and inhibitory neuronal networks resembling the composition of the human cortex. These cultures and organoids recapitulate neuronal populations representative of the six cortical layers and a balanced excitatory and inhibitory network that is functional and homeostatically stable. To determine whether hiPSC-derived neurons can integrate and retain physiologic activities in vivo, we labeled hiPSCs with red fluorescent protein (RFP) and introduced hiPSC-derived neural progenitors to rat brains. Efficient neural induction, followed by differentiation resulted in a RFP+ neural population with traits of forebrain identity and a balanced synaptic activity composed of both excitatory neurons and inhibitory interneurons. Ten weeks after transplantation, grafted cells structurally integrated into the rat forebrain. Remarkably, these hiPSC-derived neurons were able to fire, exhibiting both excitatory and inhibitory postsynaptic currents, which culminates in the establishment of neuronal connectivity with the host circuitry. This study demonstrates that neural progenitors derived from hiPSCs can differentiate into functional cortical neurons and can participate in neural network activity through functional synaptic integration in vivo, thereby contributing to information processing.",
keywords = "Balanced excitatory and inhibitory network, HiPSC-derived neurons",
author = "Xiling Yin and Xu, {Jin Chong} and Cho, {Gun Sik} and Chulan Kwon and Dawson, {Ted M.} and Dawson, {Valina L.}",
note = "Funding Information: This work was supported by Maryland Stem Cell Research Fund Grant 2009-MSCRFII-0125 to V.L.D; Grant 2013-MSCRF-0054 to J.-C. X.; and Grant 2015-MSCRFI-1622 to C.K. National Heart, Lung, and Blood Institute/National Institutes of Health (NIH) Grant R01-HL-111198, and Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH Grant R01-HD-086026 to C.K. Funding Information: Received April 17, 2019; accepted August 8, 2019; First published August 14, 2019. The authors declare no competing financial interests. Author contributions: X.Y., C.K., T.M.D., and V.L.D. designed research; X.Y., J.-C.X., and G.-s.C. performed research; X.Y., J.-C.X., and G.-s.C. analyzed data; X.Y., T.M.D., and V.L.D. wrote the paper. This work was supported by Maryland Stem Cell Research Fund Grant 2009-MSCRFII-0125 to V.L.D; Grant 2013-MSCRF-0054 to J.-C. X.; and Grant 2015-MSCRFI-1622 to C.K. National Heart, Lung, and Blood Institute/National Institutes of Health (NIH) Grant R01-HL-111198, and Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH Grant R01-HD-086026 to C.K. *X.Y. and J.-C.X. contributed equally to this work. Correspondence should be addressed to Valina L. Dawson at Vdawson@jhmi.edu or Ted M. Dawson at Tdawson@jhmi.edu. https://doi.org/10.1523/ENEURO.0148-19.2019 Copyright {\textcopyright} 2019 Yin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. Publisher Copyright: {\textcopyright} 2019 Yin et al.",
year = "2019",
month = jul,
day = "1",
doi = "10.1523/ENEURO.0148-19.2019",
language = "English (US)",
volume = "6",
journal = "eNeuro",
issn = "2373-2822",
publisher = "Society for Neuroscience",
number = "4",
}