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Connecting single neuron transcriptomes to the projectome in mouse visual cortex

Connecting single neuron transcriptomes to the projectome in mouse visual cortex

来源:bioRxiv_logobioRxiv
英文摘要

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 morpho-electric-transcriptomic (MET)-types; in parallel, we re- constructed 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 vari- ations 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.

Huang Zili、Hill Dijon、Liang Elizabeth、Yao Zizhen、Wang Yun、Mallory Matt、Lee Brian R.、Kuo Hsienchi、Kuang Xiuli、Mann Rusty、Ahmadinia Leila、Alfiler Lauren、Baker Katherine S.、Bickley Kris、Bohn Phil、Boyer Gabriella、Chen Natalie、Chen Chao、Chvilicek Maggie、de Frates Rebecca、Farrell Colin、Hadley Kristen、Kim Lisa、Lee Changkyu、Leon Arielle、Lesnar Phil、Li Anan、Li Yaoyao、Maxwell Michelle、McGraw Medea、McMillen Delissa A.、Oldre Aaron、Sulc Josef、Tieu Michael、Trinh Jessica、Walker Miranda、Wang Micheal、Wilson Julia A.、Xiong Wei、Lein Ed S.、Kalmbach Brian E.、Gong Hui、Popovich Zoran、Potekhina Lydia、Rajanbabu Ram、Ransford Shea、Sandman David、Siverts La'Akea、Slaughterbeck Cliff、Smith Kimberly A.、Stoecklin Michelle、Park Daniel、Bertagnolli Darren、Hawrylycz Mike、Hirokawa Karla E.、DePartee Maxwell、Daigle Tanya L.、Sevigny Josh、Bomben Jasmine、Sumbul Uygar、Johnson Katelyn、Wanner Adrian、Shulga Lyudmila、Berg Jim、Bannick Sarah、Dawes Tim、Ting Jonathan、Gouwens Nathan W.、Cahoon Alex、Kruse Lauren、Zeng Hongkui、Dee Nick、Esposito Luke、Vumbaco David、Gary Amanda、Link Katie、Gala Rohan、Kebede Sara、Ruiz Augustin、El-Hifnawi Laila、Budzillo Agata、Ng Lindsay、Collman Forrest、Chen Kai、Reding Melissa、Sorensen Staci A.、Waters Jack、Mukora Alice、Henry Alex、Tasic Bosiljka、Gamlin Clare、Gu Hong、Sunkin Susan M.、Egdorf Tom、Gliko Olga、Goldy Jeff、Jarsky Tim、Vargas Sara、Brouner Krissy、Luo Qingming、Juneau Zoe、Pom Christina Alice、Ng Lydia、Yao Shenqin、Dalley Rachel、Williams Grace、Baftizadeh Fahimeh

10.1101/2023.11.25.568393

生物科学研究方法、生物科学研究技术细胞生物学分子生物学

Huang Zili,Hill Dijon,Liang Elizabeth,Yao Zizhen,Wang Yun,Mallory Matt,Lee Brian R.,Kuo Hsienchi,Kuang Xiuli,Mann Rusty,Ahmadinia Leila,Alfiler Lauren,Baker Katherine S.,Bickley Kris,Bohn Phil,Boyer Gabriella,Chen Natalie,Chen Chao,Chvilicek Maggie,de Frates Rebecca,Farrell Colin,Hadley Kristen,Kim Lisa,Lee Changkyu,Leon Arielle,Lesnar Phil,Li Anan,Li Yaoyao,Maxwell Michelle,McGraw Medea,McMillen Delissa A.,Oldre Aaron,Sulc Josef,Tieu Michael,Trinh Jessica,Walker Miranda,Wang Micheal,Wilson Julia A.,Xiong Wei,Lein Ed S.,Kalmbach Brian E.,Gong Hui,Popovich Zoran,Potekhina Lydia,Rajanbabu Ram,Ransford Shea,Sandman David,Siverts La'Akea,Slaughterbeck Cliff,Smith Kimberly A.,Stoecklin Michelle,Park Daniel,Bertagnolli Darren,Hawrylycz Mike,Hirokawa Karla E.,DePartee Maxwell,Daigle Tanya L.,Sevigny Josh,Bomben Jasmine,Sumbul Uygar,Johnson Katelyn,Wanner Adrian,Shulga Lyudmila,Berg Jim,Bannick Sarah,Dawes Tim,Ting Jonathan,Gouwens Nathan W.,Cahoon Alex,Kruse Lauren,Zeng Hongkui,Dee Nick,Esposito Luke,Vumbaco David,Gary Amanda,Link Katie,Gala Rohan,Kebede Sara,Ruiz Augustin,El-Hifnawi Laila,Budzillo Agata,Ng Lindsay,Collman Forrest,Chen Kai,Reding Melissa,Sorensen Staci A.,Waters Jack,Mukora Alice,Henry Alex,Tasic Bosiljka,Gamlin Clare,Gu Hong,Sunkin Susan M.,Egdorf Tom,Gliko Olga,Goldy Jeff,Jarsky Tim,Vargas Sara,Brouner Krissy,Luo Qingming,Juneau Zoe,Pom Christina Alice,Ng Lydia,Yao Shenqin,Dalley Rachel,Williams Grace,Baftizadeh Fahimeh.Connecting single neuron transcriptomes to the projectome in mouse visual cortex[EB/OL].(2025-03-28)[2025-05-17].https://www.biorxiv.org/content/10.1101/2023.11.25.568393.点此复制

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