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Large-field of view, high-resolution spatially
resolved transcriptomics using DNA nanoball
patterned arrays
Dr. Kira Xiaohuan Sun
BGI Australia
2022.06.16
Bulk Sequencing Single Cell Sequencing Spatial Sequencing
Pancreas
cell
Heart
cell
Blood
cell
Lung
cell
Egg
cell
Liver
cell
Muscle
cell
Kidney
cell
Bone
cell
Brain
cell
From bulk analysis to spatial context
Resolution and capture area are the major challenges
Chen et al., Cell, 2022
Stereo-seq is an in situ capture
technology providing whole
transcriptome profiling developed
by BGI based on DNA Nano Ball
(DNB) with high resolution and
large field of view.
It supports simultaneous spatial
transcriptome analysis of the
same sample in tissue, cell,
subcellular and molecular levels.
SpaTial Enhanced REsolution Omics-sequencing (Stereo-seq)
Spot size Center-to-center
Chip size
Transcripts capture spots in nanometer resolution
The density of capture spots
that catching transcripts
determines the final resolution
of spatial technology.
The chip (capture area) size
determines the range of vision.
DNB patterned array
Each spot has a unique CID
Centimeter capture size with nanometer resolution
How is Stereo-Seq performed?
Two days experiment with reasonable working hours
–from tissue embedding to cDNA lib prep
Cryostat
Microscope
Molecular lab
How is Stereo-Seq performed?
Information you can gain by Stereo-seq
in situ expressed
mRNA staining
Spatial gene
expression
profiling
Histological image
from adjacent
sections
1 demo results from gene expression
profiling analysis: clustering
1
2
3
Large FOV chips for applications to large tissues
1 X 1
1.5 X 1.3
2 X 3.5
3.5 X 5
6 X 6
Mouse olfactory bulb
= Bin3
mouse olfactory bulb (Stereo-seq, Visium, Slide-seqV2 and HDST);
E10 mouse embryo (DBiT-seq);
mouse liver (Seq-Scope)
(Cho et al., 2021b; Lebrigand et al., 2020a; Liu et al., 2020;
Stickels et al., 2021; Vickovic et al., 2019; Chen et al., 2022)
Stereo-seq outperforms existing methods in mRNA capture efficiency
O
ther product 1
O
ther product 2
O
ther product 3
O
ther product 4
O
ther product 5
Mouse olfactory bulb
Stereo-seq outperforms existing methods in mRNA capture efficiency
mouse olfactory bulb (Stereo-seq, Visium, Slide-seqV2 and HDST);
E10 mouse embryo (DBiT-seq);
mouse liver (Seq-Scope)
(Cho et al., 2021b; Lebrigand et al., 2020a; Liu et al., 2020;
Stickels et al., 2021; Vickovic et al., 2019; Chen et al., 2022) Allen Brain Atlas Database of in-situ hybridizations
Other
product 1
Other
product 2
Cellular resolution in adult mouse brain tissue is achieved by Stereo-seq
Unsupervised spatially-constrained clustering analysis
(Chen et al., 2022)
Cloud-based analysis powers visualization of spatial data
Chen et al., Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays
Cell, 2022 doi: 10.1016/j.cell.2022.04.003.
High-definition panoramic STOmics atlas of mouse organogenesis
Liu et al., Spatiotemporal mapping of gene expression landscapes and developmental trajectories during zebrafish embryogenesis
Dev. Cell, 2022 doi: 10.1016/j.devcel.2022.04.009.
Zebrafish Embryogenesis Spatiotemporal Transcriptomic Atlas by stereo-seq
http://stereomap.cngb.org/zebrafish/data_index
Wang et al., High-resolution 3D spatiotemporal transcriptomic maps of developing Drosophila embryos and larvae
Dev. Cell, 2022 doi: 10.1016/j.devcel.2022.04.006.
Spatio-temporal transcriptomic maps of Drosophila embryos and larvae
Wei et al., BioRxiv, 2021. Spatiotemporal transcriptome at single-cell resolution reveals key radial glial cell population in axolotl telencephalon
development and regeneration.
Axolotl Regenerative Telencehpalon Interpretation by Stereo-seq
Wu, Liang, et al. bioRxiv (2021). Spatially-resolved transcriptomics analyses of invasive fronts in solid tumors.
https://www.biorxiv.org/content/10.1101/2021.10.21.465135v1
A
B C
Spatially-resolved transcriptomics analyses of invasive fronts in solid tumors
Large-field, high-res spatial transcriptomics using DNA nanoball arrays

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Large-field, high-res spatial transcriptomics using DNA nanoball arrays

  • 1. Large-field of view, high-resolution spatially resolved transcriptomics using DNA nanoball patterned arrays Dr. Kira Xiaohuan Sun BGI Australia 2022.06.16
  • 2. Bulk Sequencing Single Cell Sequencing Spatial Sequencing Pancreas cell Heart cell Blood cell Lung cell Egg cell Liver cell Muscle cell Kidney cell Bone cell Brain cell From bulk analysis to spatial context
  • 3. Resolution and capture area are the major challenges Chen et al., Cell, 2022
  • 4. Stereo-seq is an in situ capture technology providing whole transcriptome profiling developed by BGI based on DNA Nano Ball (DNB) with high resolution and large field of view. It supports simultaneous spatial transcriptome analysis of the same sample in tissue, cell, subcellular and molecular levels. SpaTial Enhanced REsolution Omics-sequencing (Stereo-seq)
  • 5. Spot size Center-to-center Chip size Transcripts capture spots in nanometer resolution The density of capture spots that catching transcripts determines the final resolution of spatial technology. The chip (capture area) size determines the range of vision.
  • 6. DNB patterned array Each spot has a unique CID Centimeter capture size with nanometer resolution
  • 7. How is Stereo-Seq performed?
  • 8. Two days experiment with reasonable working hours –from tissue embedding to cDNA lib prep Cryostat Microscope Molecular lab How is Stereo-Seq performed?
  • 9. Information you can gain by Stereo-seq in situ expressed mRNA staining Spatial gene expression profiling Histological image from adjacent sections 1 demo results from gene expression profiling analysis: clustering 1 2 3
  • 10. Large FOV chips for applications to large tissues 1 X 1 1.5 X 1.3 2 X 3.5 3.5 X 5 6 X 6
  • 11. Mouse olfactory bulb = Bin3 mouse olfactory bulb (Stereo-seq, Visium, Slide-seqV2 and HDST); E10 mouse embryo (DBiT-seq); mouse liver (Seq-Scope) (Cho et al., 2021b; Lebrigand et al., 2020a; Liu et al., 2020; Stickels et al., 2021; Vickovic et al., 2019; Chen et al., 2022) Stereo-seq outperforms existing methods in mRNA capture efficiency O ther product 1 O ther product 2 O ther product 3 O ther product 4 O ther product 5
  • 12. Mouse olfactory bulb Stereo-seq outperforms existing methods in mRNA capture efficiency mouse olfactory bulb (Stereo-seq, Visium, Slide-seqV2 and HDST); E10 mouse embryo (DBiT-seq); mouse liver (Seq-Scope) (Cho et al., 2021b; Lebrigand et al., 2020a; Liu et al., 2020; Stickels et al., 2021; Vickovic et al., 2019; Chen et al., 2022) Allen Brain Atlas Database of in-situ hybridizations Other product 1 Other product 2
  • 13. Cellular resolution in adult mouse brain tissue is achieved by Stereo-seq Unsupervised spatially-constrained clustering analysis (Chen et al., 2022)
  • 14. Cloud-based analysis powers visualization of spatial data
  • 15. Chen et al., Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays Cell, 2022 doi: 10.1016/j.cell.2022.04.003. High-definition panoramic STOmics atlas of mouse organogenesis
  • 16. Liu et al., Spatiotemporal mapping of gene expression landscapes and developmental trajectories during zebrafish embryogenesis Dev. Cell, 2022 doi: 10.1016/j.devcel.2022.04.009. Zebrafish Embryogenesis Spatiotemporal Transcriptomic Atlas by stereo-seq http://stereomap.cngb.org/zebrafish/data_index
  • 17. Wang et al., High-resolution 3D spatiotemporal transcriptomic maps of developing Drosophila embryos and larvae Dev. Cell, 2022 doi: 10.1016/j.devcel.2022.04.006. Spatio-temporal transcriptomic maps of Drosophila embryos and larvae
  • 18. Wei et al., BioRxiv, 2021. Spatiotemporal transcriptome at single-cell resolution reveals key radial glial cell population in axolotl telencephalon development and regeneration. Axolotl Regenerative Telencehpalon Interpretation by Stereo-seq
  • 19. Wu, Liang, et al. bioRxiv (2021). Spatially-resolved transcriptomics analyses of invasive fronts in solid tumors. https://www.biorxiv.org/content/10.1101/2021.10.21.465135v1 A B C Spatially-resolved transcriptomics analyses of invasive fronts in solid tumors