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Patch-seq: Past, Present, and Future

Research output: Contribution to journalArticlepeer-review

Marcela Lipovsek, Cedric Bardy, Cathryn R. Cadwell, Kristen Hadley, Dmitry Kobak, Shreejoy J. Tripathy

Original languageEnglish
Pages (from-to)937-946
Number of pages10
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume41
Issue number5
DOIs
Published3 Feb 2021

Bibliographical note

Funding Information: M.L. was supported by a Consolidator Grant from the European Research Council (Grant 725729; FUNCOPLAN) to Matthew Grubb. C.B. was supported by the Ian Potter Foundation, the Flinders Foundation, Impact Philanthropy, Cancer Australia, and the Australian Department of Health. K.H. was supported by the Allen Institute for Brain Sciences. D.K. was supported by the Deutsche Forschungsgemeinschaft (Grant BE5601/4-1 and the Cluster of Excellence “Machine Learning—New Perspectives for Science”, EXC 2064, Project 390727645), the Federal Ministry of Education and Research (Grants FKZ 01GQ1601 and 01IS18039A), and the National Institute of Mental Health of the National Institutes of Health under Award Number U19MH114830. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. S.J.T. was supported by the CAMH Discovery Fund, the Krembil Foundation, the Kavli Foundation, the Canadian Institutes of Health Research (Grant NGN-171423), and the Natural Sciences and Engineering Research Council of Canada (Grants RGPIN-2020-05834 and DGECR-2020-00048). We thank Matthew Grubb for helpful comments on the manuscript and for kickstarting the organization of the mini-symposium. Publisher Copyright: Copyright © 2021 the authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

Single-cell transcriptomic approaches are revolutionizing neuroscience. Integrating this wealth of data with morphology and physiology, for the comprehensive study of neuronal biology, requires multiplexing gene expression data with complementary techniques. To meet this need, multiple groups in parallel have developed "Patch-seq," a modification of whole-cell patch-clamp protocols that enables mRNA sequencing of cell contents after electrophysiological recordings from individual neurons and morphologic reconstruction of the same cells. In this review, we first outline the critical technical developments that enabled robust Patch-seq experimental efforts and analytical solutions to interpret the rich multimodal data generated. We then review recent applications of Patch-seq that address novel and long-standing questions in neuroscience. These include the following: (1) targeted study of specific neuronal populations based on their anatomic location, functional properties, lineage, or a combination of these factors; (2) the compilation and integration of multimodal cell type atlases; and (3) the investigation of the molecular basis of morphologic and functional diversity. Finally, we highlight potential opportunities for further technical development and lines of research that may benefit from implementing the Patch-seq technique. As a multimodal approach at the intersection of molecular neurobiology and physiology, Patch-seq is uniquely positioned to directly link gene expression to brain function.

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