A three-dimensional single-cell-resolution whole-brain atlas using CUBIC-X expansion microscopy and tissue clearing

Tatsuya C. Murakami; Tomoyuki Mano; Shu Saikawa; Shuhei A. Horiguchi; Daichi Shigeta; Kousuke Baba; Hiroshi Sekiya; Yoshihiro Shimizu; Kenji F. Tanaka; Hiroshi Kiyonari; Masamitsu Iino; Hideki Mochizuki; Kazuki Tainaka; Hiroki R. Ueda

doi:10.1038/s41593-018-0109-1

A three-dimensional single-cell-resolution whole-brain atlas using CUBIC-X expansion microscopy and tissue clearing

Tatsuya C. Murakami
, Tomoyuki Mano
, Shu Saikawa
, Shuhei A. Horiguchi
, Daichi Shigeta
, Kousuke Baba
, Hiroshi Sekiya
, Yoshihiro Shimizu
, Kenji F. Tanaka
, Hiroshi Kiyonari
, Masamitsu Iino
, Hideki Mochizuki
, Kazuki Tainaka
, Hiroki R. Ueda

Division of Brain Sciences

Research output: Contribution to journal › Article › peer-review

249 Citations (Scopus)

Abstract

A three-dimensional single-cell-resolution mammalian brain atlas will accelerate systems-level identification and analysis of cellular circuits underlying various brain functions. However, its construction requires efficient subcellular-resolution imaging throughout the entire brain. To address this challenge, we developed a fluorescent-protein-compatible, whole-organ clearing and homogeneous expansion protocol based on an aqueous chemical solution (CUBIC-X). The expanded, well-cleared brain enabled us to construct a point-based mouse brain atlas with single-cell annotation (CUBIC-Atlas). CUBIC-Atlas reflects inhomogeneous whole-brain development, revealing a significant decrease in the cerebral visual and somatosensory cortical areas during postnatal development. Probabilistic activity mapping of pharmacologically stimulated Arc-dVenus reporter mouse brains onto CUBIC-Atlas revealed the existence of distinct functional structures in the hippocampal dentate gyrus. CUBIC-Atlas is shareable by an open-source web-based viewer, providing a new platform for whole-brain cell profiling.

Original language	English
Pages (from-to)	625-637
Number of pages	13
Journal	Nature Neuroscience
Volume	21
Issue number	4
DOIs	https://doi.org/10.1038/s41593-018-0109-1
Publication status	Published - 2018 Apr 1

ASJC Scopus subject areas

General Neuroscience

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Murakami, T. C., Mano, T., Saikawa, S., Horiguchi, S. A., Shigeta, D., Baba, K., Sekiya, H., Shimizu, Y., Tanaka, K. F., Kiyonari, H., Iino, M., Mochizuki, H., Tainaka, K., & Ueda, H. R. (2018). A three-dimensional single-cell-resolution whole-brain atlas using CUBIC-X expansion microscopy and tissue clearing. Nature Neuroscience, 21(4), 625-637. https://doi.org/10.1038/s41593-018-0109-1

Murakami, TC, Mano, T, Saikawa, S, Horiguchi, SA, Shigeta, D, Baba, K, Sekiya, H, Shimizu, Y, Tanaka, KF, Kiyonari, H, Iino, M, Mochizuki, H, Tainaka, K & Ueda, HR 2018, 'A three-dimensional single-cell-resolution whole-brain atlas using CUBIC-X expansion microscopy and tissue clearing', Nature Neuroscience, vol. 21, no. 4, pp. 625-637. https://doi.org/10.1038/s41593-018-0109-1

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abstract = "A three-dimensional single-cell-resolution mammalian brain atlas will accelerate systems-level identification and analysis of cellular circuits underlying various brain functions. However, its construction requires efficient subcellular-resolution imaging throughout the entire brain. To address this challenge, we developed a fluorescent-protein-compatible, whole-organ clearing and homogeneous expansion protocol based on an aqueous chemical solution (CUBIC-X). The expanded, well-cleared brain enabled us to construct a point-based mouse brain atlas with single-cell annotation (CUBIC-Atlas). CUBIC-Atlas reflects inhomogeneous whole-brain development, revealing a significant decrease in the cerebral visual and somatosensory cortical areas during postnatal development. Probabilistic activity mapping of pharmacologically stimulated Arc-dVenus reporter mouse brains onto CUBIC-Atlas revealed the existence of distinct functional structures in the hippocampal dentate gyrus. CUBIC-Atlas is shareable by an open-source web-based viewer, providing a new platform for whole-brain cell profiling.",

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A three-dimensional single-cell-resolution whole-brain atlas using CUBIC-X expansion microscopy and tissue clearing

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