Connecting single-cell transcriptomes to projectomes in mouse visual
cortex
Author:
Sorensen Staci A.ORCID, Gouwens Nathan W.ORCID, Wang Yun, Mallory MattORCID, Budzillo AgataORCID, Dalley RachelORCID, Lee Brian, Gliko OlgaORCID, Kuo Hsien-chi, Kuang XiuliORCID, Mann RustyORCID, Ahmadinia Leila, Alfiler Lauren, Baftizadeh FahimehORCID, Baker KatherineORCID, Bannick Sarah, Bertagnolli DarrenORCID, Bickley KrisORCID, Bohn Phil, Brown Dillan, Bomben JasmineORCID, Brouner KrissyORCID, Chen Chao, Chen KaiORCID, Chvilicek Maggie, Collman ForrestORCID, Daigle TanyaORCID, Dawes Tim, de Frates RebeccaORCID, Dee NickORCID, DePartee Maxwell, Egdorf TomORCID, El-Hifnawi Laila, Enstrom Rachel, Esposito LukeORCID, Farrell ColinORCID, Gala RohanORCID, Glomb Andrew, Gamlin ClareORCID, Gary AmandaORCID, Goldy JeffORCID, Gu HongORCID, Hadley KristenORCID, Hawrylycz MikeORCID, Henry AlexORCID, Hill DijonORCID, Hirokawa Karla E.ORCID, Huang ZiliORCID, Johnson Katelyn, Juneau Zoe, Kebede SaraORCID, Kim LisaORCID, Lee ChangkyuORCID, Lesnar PhilORCID, Li Anan, Glomb Andrew, Li YaoyaoORCID, Liang ElizabethORCID, Link Katie, Maxwell MichelleORCID, McGraw MedeaORCID, McMillen Delissa A.ORCID, Mukora AliceORCID, Ng Lindsay, Ochoa Thomas, Oldre AaronORCID, Park DanielORCID, Pom Christina AliceORCID, Popovich Zoran, Potekhina LydiaORCID, Rajanbabu Ram, Ransford SheaORCID, Reding MelissaORCID, Ruiz AugustinORCID, Sandman DavidORCID, Siverts La’AkeaORCID, Smith Kimberly A.ORCID, Stoecklin Michelle, Sulc JosefORCID, Tieu MichaelORCID, Ting JonathanORCID, Trinh JessicaORCID, Vargas Sara, Vumbaco Dave, Walker MirandaORCID, Wang MichealORCID, Wanner AdrianORCID, Waters JackORCID, Williams GraceORCID, Wilson JuliaORCID, Xiong Wei, Lein EdORCID, Berg JimORCID, Kalmbach BrianORCID, Yao Shenqin, Gong HuiORCID, Luo QingmingORCID, Ng LydiaORCID, Sümbül UygarORCID, Jarsky TimORCID, Yao ZizhenORCID, Tasic BosiljkaORCID, Zeng HongkuiORCID
Abstract
Abstract
The mammalian brain is composed of diverse neuron types that play different
functional roles. Recent single-cell RNA sequencing approaches have led to a
whole brain taxonomy of transcriptomically-defined cell types, yet cell type
definitions that include multiple cellular properties can offer additional
insights into a neuron’s role in brain circuits. While the Patch-seq method can
investigate how transcriptomic properties relate to the local morphological and
electrophysiological properties of cell types, linking transcriptomic identities
to long-range projections is a major unresolved challenge. To address this, we
collected coordinated Patch-seq and whole brain morphology data sets of
excitatory neurons in mouse visual cortex. From the Patch-seq data, we defined
16 integrated morphoelectric-transcriptomic (MET)-types; in parallel, we
reconstructed the complete morphologies of 300 neurons. We unified the two data
sets with a multi-step classifier, to integrate cell type assignments and
interrogate cross-modality relationships. We find that transcriptomic variations
within and across MET-types correspond with morphological and
electrophysiological phenotypes. In addition, this variation, along with the
anatomical location of the cell, can be used to predict the projection targets
of individual neurons. We also shed new light on infragranular cell types and
circuits, including cell-type-specific, interhemispheric projections. With this
approach, we establish a comprehensive, integrated taxonomy of excitatory neuron
types in mouse visual cortex and create a system for integrated,
high-dimensional cell type classification that can be extended to the whole
brain and potentially across species.
Publisher
Cold Spring Harbor Laboratory
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