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Integrated spatial genomics in tissues reveals invariant and cell type dependent nuclear architecture

Takei, Yodai and Zheng, Shiwei and Yun, Jina and Shah, Sheel and Pierson, Nico and White, Jonathan and Schindler, Simone and Tischbirek, Carsten and Yuan, Guo-Cheng and Cai, Long (2021) Integrated spatial genomics in tissues reveals invariant and cell type dependent nuclear architecture. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20210430-091508303

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Abstract

Nuclear architecture in tissues can arise from cell-type specific organization of nuclear bodies, chromatin states and chromosome structures. However, the lack of genome-wide measurements to interrelate such modalities within single cells limits our overall understanding of nuclear architecture. Here, we demonstrate integrated spatial genomics in the mouse brain cortex, imaging thousands of genomic loci along with RNAs and subnuclear markers simultaneously in individual cells. We revealed chromatin fixed points, combined with cell-type specific organization of nuclear bodies, arrange the interchromosomal organization and radial positioning of chromosomes in diverse cell types. At the sub-megabase level, we uncovered a collection of single-cell chromosome domain structures, including those for the active and inactive X chromosomes. These results advance our understanding of single-cell nuclear architecture in complex tissues.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2021.04.26.441547DOIDiscussion Paper
https://github.com/CaiGroup/dna-seqfish-plus-tissueRelated ItemCode
ORCID:
AuthorORCID
Zheng, Shiwei0000-0001-6682-6743
Pierson, Nico0000-0002-2451-0633
White, Jonathan0000-0002-7009-3332
Yuan, Guo-Cheng0000-0002-2283-4714
Cai, Long0000-0002-7154-5361
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. This version posted April 27, 2021. We thank N. Ollikainen and M. Guttman for help with Hi-C analysis; R.J. Oakey for providing the processed ChIP-seq data; C.-H.L. Eng for helpful discussion; C. Karp for making custom-made flow cells; L. Sanchez and E. Buitrago-Delgado for help with the perfusion setup; I. Strazhnik for help with figures; A. Anderson for help with the manuscript. This work was supported by NIH 4DN DA047732 and supplement (L.C.), and the Paul G. Allen Frontiers Foundation Discovery Center (L.C.). Author contributions: Y.T. and L.C. conceived the idea and designed experiments. Y.T. designed probes with input from C.T.. Y.T., J.Y., and S.Schindler prepared and validated experimental materials. Y.T. performed imaging experiments. Y.T., S.Shah., N.P., and J.W. wrote image processing scripts, and Y.T. performed image processing. Y.T., S.Z., and L.C. analysed data with input from G.-C.Y.. Y.T. and L.C. wrote the manuscript with input from S.Z., C.T., and G.-C.Y.. L.C. supervised all aspects of the projects. Competing interests: L.C. is a co-founder of Spatial Genomics Inc. Data and materials availability: The custom written scripts used in this study are available in a Github repository (https://github.com/CaiGroup/dna-seqfish-plus-tissue). The source data and processed data from this study are available in a Zenodo repository (55).
Funders:
Funding AgencyGrant Number
NIH4DN DA047732
Paul G. Allen Family FoundationUNSPECIFIED
Record Number:CaltechAUTHORS:20210430-091508303
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210430-091508303
Official Citation:Integrated spatial genomics in tissues reveals invariant and cell type dependent nuclear architecture. Yodai Takei, Shiwei Zheng, Jina Yun, Sheel Shah, Nico Pierson, Jonathan White, Simone Schindler, Carsten Tischbirek, Guo-Cheng Yuan, Long Cai. bioRxiv 2021.04.26.441547; doi: https://doi.org/10.1101/2021.04.26.441547
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108898
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:30 Apr 2021 16:57
Last Modified:30 Apr 2021 16:57

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