Embryo-scale, single-cell spatial transcriptomics
Abstract
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.
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 protocols.io (36–38).Attached Files
Supplemental Material - abb9536-Srivatsan-SM-Data-File-S1.txt
Supplemental Material - abb9536-Srivatsan-SM-Data-File-S2.zip
Supplemental Material - abb9536-Srivatsan-SM-Data-File-S3.tsv
Supplemental Material - abb9536-Srivatsan-SM-Reproducibility-Checklist.pdf
Supplemental Material - abb9536-Srivatsan-SM.pdf
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Additional details
- Eprint ID
- 109730
- Resolver ID
- CaltechAUTHORS:20210707-140048718
- 1U54HL145611
- NIH
- UM1HG011586
- NIH
- 1R01HG010632
- NIH
- DP2HL137188
- NIH
- T32EB1650
- NIH
- SP1532/3-1
- Deutsche Forschungsgemeinschaft (DFG)
- SP1532/4-1
- Deutsche Forschungsgemeinschaft (DFG)
- SP1532/5-1
- Deutsche Forschungsgemeinschaft (DFG)
- Brotman Baty Institute for Precision Medicine
- Paul G. Allen Family Foundation
- Washington Research Foundation
- Howard Hughes Medical Institute (HHMI)
- Created
-
2021-07-08Created from EPrint's datestamp field
- Updated
-
2021-07-08Created from EPrint's last_modified field