Single-cell analysis of diversity in human stem cell-derived neurons
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Abstract
Neural stem and progenitor cells produce one of the most remarkable organs in nature, the human brain. Among neural stem cell progeny, post-mitotic neurons are likewise remarkably diverse. Single-cell transcriptomic approaches are now cataloging a long-sought-after molecular taxonomy of neuronal diversity in the brain. Contemporary single-cell omic classifications of neuronal diversity build from electrophysiological approaches that for decades have measured and cataloged diverse biophysical properties of single neurons. With the widespread application of human pluripotent stem cell-based models of neurogenesis to investigate disease pathology and to develop new drugs, a high-resolution understanding of neuronal diversity in vivo is essential to benchmark the state of in vitro models of human neurological disease.
Keywords
Neural development Neuronal diversity Single-cell analysis Neural stem cells Pluripotent stem cellsNotes
Acknowledgements
We thank M. Beenhakker for helpful insights into the history of the patch-clamp technique and assessment of neuronal diversity by electrophysiological methods. We also acknowledge that the single-cell field is rapidly evolving and apologize, in advance, to many colleagues whose advances in single-cell measurement of neuronal diversity will undoubtably be reported after this review was prepared. This work was supported by NIMH U01 MH106882 to M.J.M., NIGMS T32 GM008328-24 to L.J.H., and T32 GM008136-30 to N.M.
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