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.
Original language | English |
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Article number | eadf6484 |
Pages (from-to) | 1-16 |
Number of pages | 17 |
Journal | Science (New York, N.Y.) |
Volume | 382 |
Issue number | 6667 |
Early online date | 13 Oct 2023 |
DOIs | |
Publication status | Published - Oct 2023 |
Funding
We thank the Allen Institute founder, P. G. Allen, for his vision, encouragement, and support. We additionally acknowledge support and input from our remaining U01 BRAIN grant consortium colleagues as well as various Allen Institute teams including Tissue Procurement and Tissue Processing, Viral Technology, Neuroanatomy, Histology and Reagent Prep, Imaging, Rseq core, Molecular Genetics, Program Management, Human Cell Types, In Vitro Single Cell Characterization, Data and Technology, Engineering, Transcriptomics, and Genomics. We also thank our Seattle-, Amsterdam-, and Szeged-area hospital partners for support and assistance with neurosurgical tissue procurement. This publication was supported by and coordinated through the BICCN. This publication is part of the Human Cell Atlas (www.humancellatlas.org/publications/). The research reported in this publication was supported by the National Institute of Mental Health (NIMH) of the National Institutes of Health (NIH) BRAIN Initiative awards 1RF1MH114126 and UG3MH120095 (J.T.T., B.P.L., and E.S.L.), BRAIN Initiative Cell Census Network award U01MH114812 (E.S.L., H.D.M., and G.T.), and by NIMH of the NIH award 1RF1MH128778 (S.A.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was also supported in part by The Nancy and Buster Alvord Endowment (C.D.K.); grant 945539 (Human Brain Project SGA3) from the European Union’s Horizon 2020 Framework Programme for Research and Innovation (H.D.M.); European Research Council advanced grant “fasthumanneuron” 101093198 (H.D.M.); the Dutch Research Council (NWO) Open Competition (ENW-M2) grant OCENW. M20.285 (C.P.J.d.K.); the NWO Gravitation program BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (NWO: 024.004.012); VI.Vidi.213.014 grant from the Dutch Research Council (N.A.G.); the Danish Cancer Society grants R304-A17698-B5570 and R295-A16770 (A.R.K.); The Lundbeck Foundation grant R325-2019-1490 (A.R.K. and A.O.); the Independent Research Fund Denmark grants 9039-00307B (A.R.K.) and DFF-37741 (W.H.H.); and National Research, Development, and Innovation Office grants KKP 133807 Élvonal, ÚNKP-20-5-SZTE-681, TKP2021-EGA-09, TKP-2021-EGA-28, and 2019-2.1.7-ERA-NET-2022-00038; and Eötvös Loránd Research Network grants ELKH-SZTE Agykérgi Neuronhálózatok Kutatócsoport and KÖ-36/2021 (G.T.).
Funders | Funder number |
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ELKH-SZTE Agykérgi Neuronhálózatok Kutatócsoport | KÖ-36/2021 |
ENW-M2 | 024.004.012 |
European Union’s Horizon 2020 Framework Programme for Research and Innovation | |
National Institutes of Health | UG3MH120095, U01MH114812, 1RF1MH114126, 1RF1MH128778 |
National Institute of Mental Health | |
Nancy and Buster Alvord Endowment | 945539 |
Kræftens Bekæmpelse | R295-A16770, R304-A17698-B5570 |
Allen Institute | |
European Research Council | 101093198 |
Nederlandse Organisatie voor Wetenschappelijk Onderzoek | |
Lundbeck Foundation | R325-2019-1490 |
Danmarks Frie Forskningsfond | DFF-37741, 9039-00307B |
National Research, Development and Innovation Office | 2019-2.1.7-ERA-NET-2022-00038, KKP 133807, TKP-2021-EGA-28, ÚNKP-20-5-SZTE-681, TKP2021-EGA-09 |