快速GABA能神经元病毒遗传标记加上Patch-seq(膜片钳电生理加单细胞RNA测序)在人脑切片中进行采样,从而可靠地定位和分析GABA能神经元亚类和个体转录组类型。这一特性阐明了PVALB和SST亚类之间的转换,揭示了丰富的转录组类型内的形态异质性,鉴定了灵长类特化双束细胞(DBC)的多种空间不同类型,并揭示了同源小鼠和人类新皮层GABA能神经元类型之间的细胞差异。
这些结果强调了多模态表型表征对于改进新兴转录组细胞类型分类,以及理解人类脑细胞类型的保守和特化细胞特性的重要性。
据介绍,人类皮层转录组学研究揭示了γ-氨基丁酸产生(GABA能)神经元从亚类到高多样性的更颗粒型的分层组织。
附:英文原文
Title: Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex
Author: Brian R. Lee, Rachel Dalley, Jeremy A. Miller, Thomas Chartrand, Jennie Close, Rusty Mann, Alice Mukora, Lindsay Ng, Lauren Alfiler, Katherine Baker, Darren Bertagnolli, Krissy Brouner, Tamara Casper, Eva Csajbok, Nicholas Donadio, Stan L.W. Driessens, Tom Egdorf, Rachel Enstrom, Anna A. Galakhova, Amanda Gary, Emily Gelfand, Jeff Goldy, Kristen Hadley, Tim S. Heistek, Dijon Hill, Wen-Hsien Hou, Nelson Johansen, Nik Jorstad, Lisa Kim, Agnes Katalin Kocsis, Lauren Kruse, Michael Kunst, Gabriela León, Brian Long, Matthew Mallory, Michelle Maxwell, Medea McGraw, Delissa McMillen, Erica J. Melief, Gabor Molnar, Marty T. Mortrud, Dakota Newman, Julie Nyhus, Ximena Opitz-Araya, Attila Ozsvár, Trangthanh Pham, Alice Pom, Lydia Potekhina, Ram Rajanbabu, Augustin Ruiz, Susan M. Sunkin, Ildikó Szts, Naz Taskin, Bargavi Thyagarajan, Michael Tieu, Jessica Trinh, Sara Vargas, David Vumbaco, Femke Waleboer, Sarah Walling-Bell, Natalie Weed, Grace Williams, Julia Wilson, Shenqin Yao, Thomas Zhou, Pál Barzó, Trygve Bakken, Charles Cobbs, Nick Dee, Richard G. Ellenbogen, Luke Esposito, Manuel Ferreira, Nathan W. Gouwens, Benjamin Grannan, Ryder P. Gwinn, Jason S. Hauptman, Rebecca Hodge, Tim Jarsky, C. Dirk Keene, Andrew L. Ko, Anders Rosendal Korshoej, Boaz P. Levi, Kaare Meier, Jeffrey G. Ojemann, Anoop Patel, Jacob Ruzevick, Daniel L. Silbergeld, Kimberly Smith, Jens Christian Srensen, Jack Waters, Hongkui Zeng, Jim Berg, Marco Capogna, Natalia A. Goriounova, Brian Kalmbach, Christiaan P.J. de Kock, Huib D. Mansvelder, Staci A. Sorensen, Gabor Tamas, Ed S. Lein, Jonathan T. Ting
Issue&Volume: 2023-10-13
Abstract: Human cortex transcriptomic studies have revealed a hierarchical organization of γ-aminobutyric acid–producing (GABAergic) neurons from subclasses to a high diversity of more granular types. Rapid GABAergic neuron viral genetic labeling plus Patch-seq (patch-clamp electrophysiology plus single-cell RNA sequencing) sampling in human brain slices was used to reliably target and analyze GABAergic neuron subclasses and individual transcriptomic types. This characterization elucidated transitions between PVALB and SST subclasses, revealed morphological heterogeneity within an abundant transcriptomic type, identified multiple spatially distinct types of the primate-specialized double bouquet cells (DBCs), and shed light on cellular differences between homologous mouse and human neocortical GABAergic neuron types. These results highlight the importance of multimodal phenotypic characterization for refinement of emerging transcriptomic cell type taxonomies and for understanding conserved and specialized cellular properties of human brain cell types.
DOI: adf6484
Source: https://www.science.org/doi/10.1126/science.adf6484
