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A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation

View ORCID ProfileZizhen Yao, View ORCID ProfileThuc Nghi Nguyen, View ORCID ProfileCindy T. J. van Velthoven, View ORCID ProfileJeff Goldy, View ORCID ProfileAdriana E. Sedeno-Cortes, View ORCID ProfileFahimeh Baftizadeh, View ORCID ProfileDarren Bertagnolli, View ORCID ProfileTamara Casper, View ORCID ProfileKirsten Crichton, View ORCID ProfileSong-Lin Ding, View ORCID ProfileOlivia Fong, Emma Garren, View ORCID ProfileAlexandra Glandon, View ORCID ProfileJames Gray, View ORCID ProfileLucas T. Graybuck, Daniel Hirschstein, View ORCID ProfileMatthew Kroll, View ORCID ProfileKanan Lathia, View ORCID ProfileBoaz Levi, View ORCID ProfileDelissa McMillen, Stephanie Mok, View ORCID ProfileThanh Pham, View ORCID ProfileQingzhong Ren, View ORCID ProfileChristine Rimorin, View ORCID ProfileNadiya Shapovalova, View ORCID ProfileJosef Sulc, View ORCID ProfileSusan M. Sunkin, View ORCID ProfileMichael Tieu, View ORCID ProfileAmy Torkelson, View ORCID ProfileHerman Tung, View ORCID ProfileKatelyn Ward, View ORCID ProfileNick Dee, View ORCID ProfileKimberly A. Smith, View ORCID ProfileBosiljka Tasic, View ORCID ProfileHongkui Zeng
doi: https://doi.org/10.1101/2020.03.30.015214
Zizhen Yao
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Thuc Nghi Nguyen
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Cindy T. J. van Velthoven
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Jeff Goldy
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Adriana E. Sedeno-Cortes
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Fahimeh Baftizadeh
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Darren Bertagnolli
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Tamara Casper
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Kirsten Crichton
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Song-Lin Ding
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Olivia Fong
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Emma Garren
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Alexandra Glandon
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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James Gray
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Lucas T. Graybuck
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Daniel Hirschstein
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Matthew Kroll
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Kanan Lathia
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Boaz Levi
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Delissa McMillen
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Stephanie Mok
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Thanh Pham
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Qingzhong Ren
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Christine Rimorin
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Nadiya Shapovalova
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Josef Sulc
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Susan M. Sunkin
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Michael Tieu
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Amy Torkelson
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Herman Tung
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Katelyn Ward
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Nick Dee
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Kimberly A. Smith
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Bosiljka Tasic
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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Hongkui Zeng
1Allen Institute for Brain Science, Seattle, WA 98109, USA
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  • For correspondence: hongkuiz@alleninstitute.org
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SUMMARY

The isocortex and hippocampal formation are two major structures in the mammalian brain that play critical roles in perception, cognition, emotion and learning. Both structures contain multiple regions, for many of which the cellular composition is still poorly understood. In this study, we used two complementary single-cell RNA-sequencing approaches, SMART-Seq and 10x, to profile ∼1.2 million cells covering all regions in the adult mouse isocortex and hippocampal formation, and derived a cell type taxonomy comprising 379 transcriptomic types. The completeness of coverage enabled us to define gene expression variations across the entire spatial landscape without significant gaps. We found that cell types are organized in a hierarchical manner and exhibit varying degrees of discrete or continuous relatedness with each other. Such molecular relationships correlate strongly with the spatial distribution patterns of the cell types, which can be region-specific, or shared across multiple regions, or part of one or more gradients along with other cell types. Glutamatergic neuron types have much greater diversity than GABAergic neuron types, both molecularly and spatially, and they define regional identities as well as inter-region relationships. For example, we found that glutamatergic cell types between the isocortex and hippocampal formation are highly distinct from each other yet possess shared molecular signatures and corresponding layer specificities, indicating their homologous relationships. Overall, our study establishes a molecular architecture of the mammalian isocortex and hippocampal formation for the first time, and begins to shed light on its underlying relationship with the development, evolution, connectivity and function of these two brain structures.

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Posted March 31, 2020.
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A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation
Zizhen Yao, Thuc Nghi Nguyen, Cindy T. J. van Velthoven, Jeff Goldy, Adriana E. Sedeno-Cortes, Fahimeh Baftizadeh, Darren Bertagnolli, Tamara Casper, Kirsten Crichton, Song-Lin Ding, Olivia Fong, Emma Garren, Alexandra Glandon, James Gray, Lucas T. Graybuck, Daniel Hirschstein, Matthew Kroll, Kanan Lathia, Boaz Levi, Delissa McMillen, Stephanie Mok, Thanh Pham, Qingzhong Ren, Christine Rimorin, Nadiya Shapovalova, Josef Sulc, Susan M. Sunkin, Michael Tieu, Amy Torkelson, Herman Tung, Katelyn Ward, Nick Dee, Kimberly A. Smith, Bosiljka Tasic, Hongkui Zeng
bioRxiv 2020.03.30.015214; doi: https://doi.org/10.1101/2020.03.30.015214
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A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation
Zizhen Yao, Thuc Nghi Nguyen, Cindy T. J. van Velthoven, Jeff Goldy, Adriana E. Sedeno-Cortes, Fahimeh Baftizadeh, Darren Bertagnolli, Tamara Casper, Kirsten Crichton, Song-Lin Ding, Olivia Fong, Emma Garren, Alexandra Glandon, James Gray, Lucas T. Graybuck, Daniel Hirschstein, Matthew Kroll, Kanan Lathia, Boaz Levi, Delissa McMillen, Stephanie Mok, Thanh Pham, Qingzhong Ren, Christine Rimorin, Nadiya Shapovalova, Josef Sulc, Susan M. Sunkin, Michael Tieu, Amy Torkelson, Herman Tung, Katelyn Ward, Nick Dee, Kimberly A. Smith, Bosiljka Tasic, Hongkui Zeng
bioRxiv 2020.03.30.015214; doi: https://doi.org/10.1101/2020.03.30.015214

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