Cited by 666Single-cell and spatial transcriptomicsGene expression and cancer classificationMolecular Biology Techniques and Applications

Spatially resolved transcriptomes—next generation tools for tissue exploration

Open access
Asp, Michaela, Bergenstråhle, Joseph, Lundeberg, Joakim·2020·BioEssays

Abstract

Recent advances in spatially resolved transcriptomics have greatly expanded the knowledge of complex multicellular biological systems. The field has quickly expanded in recent years, and several new technologies have been developed that all aim to combine gene expression data with spatial information. The vast array of methodologies displays fundamental differences in their approach to obtain this information, and thus, demonstrate method-specific advantages and shortcomings. While the field is moving forward at a rapid pace, there are still multiple challenges presented to be addressed, including sensitivity, labor extensiveness, tissue-type dependence, and limited capacity to obtain detailed single-cell information. No single method can currently address all these key parameters. In this review, available spatial transcriptomics methods are described and their applications as well as their strengths and weaknesses are discussed. Future developments are explored and where the field is heading to is deliberated upon.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1002/bies.201900221

Cites

64 of 64 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Spatial transcriptomics has enabled characterization of fine-scale, cell-type-specific transcriptional heterogeneity within intact tissue, revealing molecular gradients not captured by region-averaged approaches.

    “More recently, spatial transcriptomics has enabled characterization of fine‐scale, cell‐type–specific transcriptional heterogeneity within intact tissue, revealing molecular gradients not captured by region‐averaged approaches. 62 , 84”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 60

  1. G. Zheng, S. Li, G. Szekely, 2017. Statistical Shape and Deformation Analysis: Methods, Implementation and Applications, Academic Press, London 2017.
  2. M.-C. Ramel, C. S. Hill, Dev. Biol. 2013, 378, 170.
  3. G. T. Reeves, N. Trisnadi, T. V. Truong, M. Nahmad, S. Katz, A. Stathopoulos, Dev. Cell 2012, 22, 544.
  4. G. Stanta, S. Bonin, Front. Med. 2018, 5, 85.
  5. M. R. Emmert-Buck, R. F. Bonner, P. D. Smith, R. F. Chuaqui, Z. Zhuang, S. R. Goldstein, R. A. Weiss, L. A. Liotta, Science 1996, 274, 998.
  6. N. L. Simone, R. F. Bonner, J. W. Gillespie, M. R. Emmert-Buck, L. A. Liottaa, Trends Genet. 1998, 14, 272.
  7. J. Chen, S. Suo, P. P. Tam, J.-.D. J. Han, G. Peng, N. Jing, Nat. Protoc. 2017, 12, 566.
  8. P. A. Combs, M. B. Eisen, PLoS One 2013, 8, e71820.
  9. J. P. Junker, E. S. Noël, V. Guryev, K. A. Peterson, G. Shah, J. Huisken, A. P. McMahon, E. Berezikov, J. Bakkers, A. dervan Oudenaarden, Cell 2014, 159, 662.
  10. T. Hashimshony, F. Wagner, N. Sher, I. Yanai, Cell Rep. 2012, 2, 666.
  11. D. Lovatt, B. K. Ruble, J. Lee, H. Dueck, T. K. Kim, S. Fisher, C. Francis, J. M. Spaethling, J. A. Wolf, M. S. Grady, A. V. Ulyanova, S. B. Yeldell, J. C. Griepenburg, P. T. Buckley, J. Kim, J. Y. Sul, I. J. Dmochowski, J. Eberwine, Nat. Methods 2014, 11, 190.
  12. C. Medaglia, A. Giladi, L. Stoler-Barak, M. De Giovanni, T. M. Salame, A. Biram, E. David, H. Li, M. Iannacone, Z. Shulman, I. Amit, Science 2017, 358, 1622.
  13. J.-C. Boisset, J. Vivié, D. Grün, M. J. Muraro, A. Lyubimova, A. van Oudenaarden, Nat. Methods 2018, 15, 547.
  14. J. G. Gall, M. L. Pardue, Proc. Natl. Acad. Sci. USA 1969, 63, 378.
  15. R. H. Singer, D. C. Ward, Proc. Natl. Acad. Sci. USA 1982, 79, 7331.
  16. A. M. Femino, F. S. Fay, K. Fogarty, R. H. Singer, Science 1998, 280, 585.
  17. A. Raj, P. Van Den Bogaard, S. Rifkin, Nat. Methods 2008, 5, 877.
  18. E. Lubeck, A. F. Coskun, T. Zhiyentayev, M. Ahmad, L. Cai, Nat. Meth- ods 2014, 11, 360.
  19. S. Shah, E. Lubeck, W. Zhou, L. Cai, Neuron 2016, 92, 342.
  20. S. Shah, E. Lubeck, M. Schwarzkopf, T. F. He, A. Greenbaum, C. H. Sohn, A. Lignell, H. M. Choi, V. Gradinaru, N. A. Pierce, L. Cai, Devel- opment 2016, 143, 2862.
  21. G. Wang, J. R. Moffitt, X. Zhuang, Sci. Rep. 2018, 8, 4847.
  22. F. Chen, A. T. Wassie, A. J. Cote, A. Sinha, S. Alon, S. Asano, E. R. Daugharthy, J. B. Chang, A. Marblestone, G. M. Church, A. Raj, E. S. Boyden, Nat. Methods 2016, 13, 679.
  23. C.-H. L. Eng, M. Lawson, Q. Zhu, R. Dries, N. Koulena, Y. Takei, J. Yun, C. Cronin, C. Karp, G. C. Yuan, L. Cai, Nature 2019, 568, 235.
  24. S. Codeluppi, L. E. Borm, A. Zeisel, G. La Manno, J. A. van Lunteren, C. I. Svensson, S. Linnarsson, Nat. Methods 2018, 15, 932.
  25. D. Clair, Bio-Techne Announces Commercial Release of RNAscope® HiPlex Assay: A Multiplex In Situ Hybridization Assay For Tissues 2016. https://investors.bio-techne.com/press-releases/detail/148/ bio-techne-announces-commercial-release-of-rnascope. Accessed month: Feb 2020.
  26. D. Schulz, V. R. T. Zanotelli, J. R. Fischer, D. Schapiro, S. Engler, X. K. Lun, H. W. Jackson, B. Bodenmiller, Cell Syst. 2018, 6, 25. e5.
  27. A. Mavropoulos, B. Allo, M. He, E. Park, D. Majonis, O. Ornatsky, Cytometry, Part A 2017, 91, 1200.
  28. J. A. Weinstein, A. Regev, F. Zhang, Cell 2019, 178, 229.
  29. R. Ke, M. Mignardi, A. Pacureanu, J. Svedlund, J. Botling, C. Wählby, M. Nilsson, Nat. Methods 2013, 10, 857.
  30. X. Qian, K. D. Harris, T. Hauling, D. Nicoloutsopoulos, A. B. Muñoz- Manchado, N. Skene, J. Hjerling-Leffler, M. Nilsson, Nat. Methods 2020, 17, 101.
  31. N. Maïno, T. Hauling, G. Cappi, N. Madaboosi, D. G. Dupouy, M. Nilsson, Sci. Rep. 2019, 9, 3542.
  32. D. Gyllborg, C. M. Langseth, X. Qian, S. M. Salas, bioRxiv 2020. https: //doi.org/10.1101/2020.02.03.931618. Accepted February 03, 2020. · DOI
  33. X. Chen, Y.-C. Sun, G. M. Church, J. H. Lee, A. M. Zador, Nucleic Acids Res. 2018, 46, e22.
  34. J. H. Lee, E. R. Daugharthy, J. Scheiman, R. Kalhor, J. L. Yang, T. C. Ferrante, R. Terry, S. S. Jeanty, C. Li, R. Amamoto, D. T. Peters, B. M. Turczyk, A. H. Marblestone, S. A. Inverso, A. Bernard, P. Mali, X. Rios, J. Aach, G. M. Church, Science 2014, 343, 1360.
  35. D. Furth, V. Hatini, J. H. Lee, bioRxiv 2019, 722819.
  36. P. L. Ståhl, F. Salmén, S. Vickovic, A. Lundmark, J. F. Navarro, J. Mag- nusson, S. Giacomello, M. Asp, J. O. Westholm, M. Huss, A. Moll- brink, S. Linnarsson, S. Codeluppi, Å. Borg, F. Pontén, P. Igor Costea, P. Sahlén, J. Mulder, O. Bergmann, J. Lundeberg, J. Frisén, Science 2016, 353, 78.
  37. S. G. Rodriques, R. R. Stickels, A. Goeva, C. A. Martin, E. Murray, C. R. Vanderburg, J. Welch, L. M. Chen, F. Chen, E. Z. Macosko, Science 2019, 363, 1463.
  38. S. Vickovic, G. Eraslan, F. Salmén, J. Klughammer, L. Stenbeck, D. Schapiro, T. Äijö, R. Bonneau, L. Bergenstråhle, J. F. Navarro, J. Gould, G. K. Griffin, B. Å, M. Ronaghi, J. Frisén, J. Lundeberg, A. Regev, P. L. Ståhl, Nat. Methods 2019, 16, 987.
  39. C. R. Merritt, G. T. Ong, S. Church, K. Barker, G. Geiss, M. Hoang, J. Jung, Y. Liang, J. McKay-Fleisch, K. Nguyen, K. Sorg, I. Sprague, C. Warren, S. Warren, Z. Zhou, D. R. Zollinger, D. L. Dunaway, G. B. Mills, J. M. Beechem, bioRxiv 2019, 559021.
  40. T. M. Van, C. U. Blank, Immuno-Oncol. Technol. 2019, 1, 11.
  41. F. M. Fazal, S. Han, K. R. Parker, P. Kaewsapsak, J. Xu, A. N. Boettiger, H. Y. Chang, A. Y. Ting, Cell 2019, 178, 473. e26.
  42. A. Padron, S. Iwasaki, N. T. Ingolia, Mol. Cell 2019, 75, 875.
  43. R. Satija, J. A. Farrell, D. Gennert, A. F. Schier, A. Regev, Nat. Biotech- nol. 2015, 33, 495.
  44. K. Achim, J. -. B. Pettit, L. R. Saraiva, D. Gavriouchkina, T. Larsson, D. Arendt, J. C. Marioni, Nat. Biotechnol. 2015, 33, 503.
  45. N. Karaiskos, P. Wahle, J. Alles, A. Boltengagen, S. Ayoub, C. Kipar, C. Kocks, N. Rajewsky, R. P. Zinzen, Science 2017, 358, 194.
  46. R. Moncada, D. Barkley, F. Wagner, M. Chiodin, J. C. Devlin, M. Baron, C. H. Hajdu, D. M. Simeone, I. Yanai, Nat. Biotechnol. 2020, 38, 333.
  47. M. Nitzan, N. Karaiskos, N. Friedman, N. Rajewsky, Nature 2019, 576, 132.
  48. D. Grün, A. van Oudenaarden, Cell 2015, 163, 799.
  49. L. Annaratone, M. Simonetti, E. Wernersson, C. Marchiò, S. Gar- nerone, M. S. Scalzo, M. Bienko, R. Chiarle, A. Sapino, N. Crosetto, Oncotarget 2017, 8, 18680.
  50. E. Lein, L. E. Borm, S. Linnarsson, Science 2017, 358, 64.
  51. M. Mignardi, A. Mezger, X. Qian, L. La Fleur, J. Botling, C. Larsson, M. Nilsson, Nucleic Acids Res. 2015, 43, e151.
  52. C. Larsson, I. Grundberg, O. Söderberg, M. Nilsson, Nat. Methods 2010, 7, 395.
  53. J. H. Lee, Wiley Interdiscip. Rev.: Syst. Biol. Med. 2017, 9, e1369.
  54. E. Z. Macosko, A. Basu, R. Satija, J. Nemesh, K. Shekhar, M. Gold- man, I. Tirosh, A. R. Bialas, N. Kamitaki, E. M. Martersteck, J. J. Trom- betta, D. A. Weitz, J. R. Sanes, A. K. Shalek, A. Regev, S. A. McCarroll, Cell 2015, 161, 1202.
  55. A. Regev, S. A. Teichmann, E. S. Lander, I. Amit, C. Benoist, E. Birney, B. Bodenmiller, P. Campbell, P. Carninci, M. Clatworthy, H. Clevers, B. Deplancke, I. Dunham, J. Eberwine, R. Eils, W. Enard, A. Farmer, L. Fugger, B. Göttgens, N. Hacohen, M. Haniffa, M. Hemberg, S. Kim, P. Klenerman, A. Kriegstein, E. Lein, S. Linnarsson, E. Lundberg, J. Lundeberg, P. Majumder, Elife 2017, 6, e27041.
  56. J. E. Rood, T. Stuart, S. Ghazanfar, T. Biancalani, E. Fisher, A. Butler, A. Hupalowska, L. Gaffney, W. Mauck, G. Eraslan, J. C. Marioni, A. Regev, R. Satija, Cell 2019, 179, 1455.
  57. R. Lopez, A. Nazaret, M. Langevin, J. Samaran, J. Regier, M. I. Jordan, N. Yosef, arXiv:190502269, 2019.
  58. S. Maniatis, T. Äijö, S. Vickovic, C. Braine, K. Kang, A. Mollbrink, D. Fagegaltier, A. Ž. S. Saarenpää, G. Saiz-Castro, M. Cuevas, A. Watters, J. Lundeberg, R. Bonneau, H. Phatnani, Science 2019, 364, 89.
  59. M. Asp, S. Giacomello, L. Larsson, C. Wu, D. Fürth, X. Qian, E. Wärdell, J. Custodio, J. Reimegård, F. Salmén, C. Österholm, P. L. Ståhl, E. Sundström, E. Åkesson, O. Bergmann, M. Bienko, A. Månsson-Broberg, M. Nilsson, C. Sylvén, J. Lundeberg, Cell 2019, 179, 1647.
  60. N. Crosetto, M. Bienko, A. Van Oudenaarden, Nat. Rev. Genet. 2015, 16, 57.

Cited by

Sorted by citations

Authors
Asp, M., Bergenstråhle, J., & Lundeberg, J.
Affiliations
Science for Life Laboratory (SE)
Corresponding author
Lundeberg, Joakim
Venue
BioEssays
Publisher
Wiley
Published
2020-05-04
Volume
42
Issue
10
Pages
e1900221-e1900221
ISSN
  • 0265-9247 (ISSN-L)
  • 1521-1878
OpenAlex
W3021920958
Cited by
666
References
64
Citations by year
2026: 101 · 2025: 109 · 2024: 161 · 2023: 109 · 2022: 89 · 2021: 80 · 2020: 17
FWCI
7.06
Type
journal article
Language
en
Open access
Locations
  • BioEssays (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Molecular Biology Techniques and Applications
Keywords
spatial transcriptomics, gene expression mapping, single-cell transcriptomics, spatial resolution, sensitivity
MeSH terms
Transcriptome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review