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Embryo-scale, single-cell spatial transcriptomics

Srivatsan, Sanjay R. and Regier, Mary C. and Barkan, Eliza and Franks, Jennifer M. and Packer, Jonathan S. and Grosjean, Parker and Duran, Madeleine and Saxton, Sarah and Ladd, Jon J. and Spielmann, Malte and Lois, Carlos and Lampe, Paul D. and Shendure, Jay and Stevens, Kelly R. and Trapnell, Cole (2021) Embryo-scale, single-cell spatial transcriptomics. Science, 373 (6550). pp. 111-117. ISSN 0036-8075. doi:10.1126/science.abb9536.

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Spatial patterns of gene expression manifest at scales ranging from local (e.g., cell-cell interactions) to global (e.g., body axis patterning). However, current spatial transcriptomics methods either average local contexts or are restricted to limited fields of view. Here, we introduce sci-Space, which retains single-cell resolution while resolving spatial heterogeneity at larger scales. Applying sci-Space to developing mouse embryos, we captured approximate spatial coordinates and whole transcriptomes of about 120,000 nuclei. We identify thousands of genes exhibiting anatomically patterned expression, leverage spatial information to annotate cellular subtypes, show that cell types vary substantially in their extent of spatial patterning, and reveal correlations between pseudotime and the migratory patterns of differentiating neurons. Looking forward, we anticipate that sci-Space will facilitate the construction of spatially resolved single-cell atlases of mammalian development.

Item Type:Article
Related URLs:
URLURL TypeDescription Materials
Srivatsan, Sanjay R.0000-0001-7282-0487
Regier, Mary C.0000-0001-9074-6604
Barkan, Eliza0000-0001-7871-4327
Franks, Jennifer M.0000-0003-2400-5431
Packer, Jonathan S.0000-0003-4025-0007
Grosjean, Parker0000-0002-2024-119X
Duran, Madeleine0000-0003-1648-2369
Saxton, Sarah0000-0002-3901-4843
Spielmann, Malte0000-0002-0583-4683
Lois, Carlos0000-0002-7305-2317
Lampe, Paul D.0000-0002-1399-2761
Shendure, Jay0000-0002-1516-1865
Stevens, Kelly R.0000-0002-4024-2990
Trapnell, Cole0000-0002-8105-4347
Additional Information:© 2021 American Association for the Advancement of Science. This is an article distributed under the terms of the Science Journals Default License. Received 30 March 2020; resubmitted 13 February 2021; Accepted 24 May 2021. We thank members of the Lampe, Stevens, Shendure, and Trapnell laboratories for critical discussions and feedback, particularly V. M. Rachleff, E. Nichols, R. Daza, J. Cao, V. Ramani, and L. Saunders. Aspects of this work were supported by the NIH (1U54HL145611 to C.T. and J.S.; UM1HG011586 to C.T. and J.S.; 1R01HG010632 to C.T. and J.S.; DP2HL137188 to K.R.S.; and T32EB1650 to S.S.), the Deutsche Forschungsgemeinschaft (SP1532/3-1;4-1;5-1 to M.S), the Brotman Baty Institute for Precision Medicine, the Paul G. Allen Frontiers Foundation (Allen Discovery Center grant to J.S. and C.T.), and the Washington Research Foundation (postdoctoral fellowship to M.C.R.). J.S. is an investigator of the Howard Hughes Medical Institute. Author contributions: S.R.S. and M.C.R. conceptualized and performed the experiments. J.L. aided in sci-Space slide fabrication with support from P.L. S.R.S. and M.C.R. performed the computational analyses with assistance from E.B., P.G., J.F., M.D., and J.P. and under the supervision of C.T. M.S. and C.L. provided critical feedback on the project. S.R.S., M.C.R., C.T., K.R.S., and J.S. wrote the manuscript with input from all authors. K.R.S., J.S., and C.T. supervised the project. Competing interests: One or more embodiments of one or more patents and patent applications filed by the University of Washington may encompass the methods, reagents, and data disclosed in this manuscript. Data and materials availability: Processed and raw data can be downloaded from the National Center for Biotechnology Information (NCBI) under GSE166692. Code used to reproduce the presented analyses is indexed on Zenodo (35). Laboratory protocols can be found on (36–38).
Funding AgencyGrant Number
Deutsche Forschungsgemeinschaft (DFG)SP1532/3-1
Deutsche Forschungsgemeinschaft (DFG)SP1532/4-1
Deutsche Forschungsgemeinschaft (DFG)SP1532/5-1
Brotman Baty Institute for Precision MedicineUNSPECIFIED
Paul G. Allen Family FoundationUNSPECIFIED
Washington Research FoundationUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:6550
Record Number:CaltechAUTHORS:20210707-140048718
Persistent URL:
Official Citation:Embryo-scale, single-cell spatial transcriptomics. Sanjay R. Srivatsan, Mary C. Regier, Eliza Barkan, Jennifer M. Franks, Jonathan S. Packer, Parker Grosjean, Madeleine Duran, Sarah Saxton, Jon J Ladd, Malte Spielmann, Carlos Lois, Paul D. Lampe, Jay Shendure, Kelly R. Stevens and Cole Trapnell. Science 373 (6550), 111-117; DOI: 10.1126/science.abb9536
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:109730
Deposited By: Tony Diaz
Deposited On:08 Jul 2021 17:20
Last Modified:08 Jul 2021 17:20

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