TY - JOUR
T1 - A three-dimensional single-cell-resolution whole-brain atlas using CUBIC-X expansion microscopy and tissue clearing
AU - Murakami, Tatsuya C.
AU - Mano, Tomoyuki
AU - Saikawa, Shu
AU - Horiguchi, Shuhei A.
AU - Shigeta, Daichi
AU - Baba, Kousuke
AU - Sekiya, Hiroshi
AU - Shimizu, Yoshihiro
AU - Tanaka, Kenji F.
AU - Kiyonari, Hiroshi
AU - Iino, Masamitsu
AU - Mochizuki, Hideki
AU - Tainaka, Kazuki
AU - Ueda, Hiroki R.
N1 - Funding Information:
tissue-swelling phenomenon, S. Shoi for helping with statistical analysis, K. Yoshida for helping with the decomposing transformation matrix, and C. Shimizu for supporting swelling experiments. We also thank H. Hayakawa and S. Jiang for supporting the preparation of a C57BL/6J mouse brain, D. Perrin and H. Yukinaga for informatics instruction, J. Kaneshiro, T. Watanabe and Olympus Engineering for helping design the microscope, T. Mitani and K. Matsumoto for reproducibility confirmation, S. Takano, S. Yamazoe and T. Tsukuda for the measurements of zeta potentials and Bitplane for instruction of Imaris 8.1.2. This work was supported by a grant from AMED-CREST (AMED/MEXT, grant number JP17gm0610006, to H.R.U.), CREST (JST/MEXT, to H.R.U.), Brain/MINDS (AMED/MEXT, grant number JP17dm0207049, to H.R.U. and H. M.), Basic Science and Platform Technology Program for Innovative Biological Medicine (AMED/MEXT, grant number JP17am0301025, to H.R.U.), Translational Research Network Program from Japan Agency for Medical Research and development (AMED, to H.M.), World Premier International Research Center Initiative (MEXT, to H.R.U), a Grant-in-Aid for Scientific Research (JSPS KAKENHI, grant number 16J05041, to T.C.M.), a Grant-in-Aid for Scientific Research (S) (JSPS KAKENHI, grant number 25221004, to H.R.U.), Grant-in-Aid for Challenging Exploratory Research (JSPS KAKENHI, grant number 16K15124, to K.T.), a Grant-in-Aid for Scientific Research on Innovative Areas (JSPS KAKENHI, grant number 23115006, to H.R.U., 15H01558, to H.M., 17H05688, to K.T.), and a Grant-in-Aid from the Naito Foundation (to K.T.).
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/4/1
Y1 - 2018/4/1
N2 - 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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=85042846320&partnerID=8YFLogxK
U2 - 10.1038/s41593-018-0109-1
DO - 10.1038/s41593-018-0109-1
M3 - Article
C2 - 29507408
AN - SCOPUS:85042846320
SN - 1097-6256
VL - 21
SP - 625
EP - 637
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 4
ER -