RT Journal Article
SR Electronic
T1 Patch-seq: Past, Present, and Future
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 937
OP 946
DO 10.1523/JNEUROSCI.1653-20.2020
VO 41
IS 5
A1 Lipovsek, Marcela
A1 Bardy, Cedric
A1 Cadwell, Cathryn R.
A1 Hadley, Kristen
A1 Kobak, Dmitry
A1 Tripathy, Shreejoy J.
YR 2021
UL http://www.jneurosci.org/content/41/5/937.abstract
AB 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.