Exploring rare cellular activity in more than one million cells by a transscale scope.
Animals
Brain
/ cytology
Calcium
/ analysis
Cells
/ cytology
Cyclic AMP
/ analysis
Dictyostelium
/ chemistry
Dogs
Entosis
Epithelial Cells
/ ultrastructure
Equipment Design
Green Fluorescent Proteins
HeLa Cells
/ chemistry
Humans
Interneurons
/ ultrastructure
Luminescent Proteins
Madin Darby Canine Kidney Cells
Mice
Microscopy, Fluorescence
/ instrumentation
Neurons
/ ultrastructure
Semiconductors
Red Fluorescent Protein
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
16 08 2021
16 08 2021
Historique:
received:
12
05
2021
accepted:
03
08
2021
entrez:
17
8
2021
pubmed:
18
8
2021
medline:
16
11
2021
Statut:
epublish
Résumé
In many phenomena of biological systems, not a majority, but a minority of cells act on the entire multicellular system causing drastic changes in the system properties. To understand the mechanisms underlying such phenomena, it is essential to observe the spatiotemporal dynamics of a huge population of cells at sub-cellular resolution, which is difficult with conventional tools such as microscopy and flow cytometry. Here, we describe an imaging system named AMATERAS that enables optical imaging with an over-one-centimeter field-of-view and a-few-micrometer spatial resolution. This trans-scale-scope has a simple configuration, composed of a low-power lens for machine vision and a hundred-megapixel image sensor. We demonstrated its high cell-throughput, capable of simultaneously observing more than one million cells. We applied it to dynamic imaging of calcium ions in HeLa cells and cyclic-adenosine-monophosphate in Dictyostelium discoideum, and successfully detected less than 0.01% of rare cells and observed multicellular events induced by these cells.
Identifiants
pubmed: 34400683
doi: 10.1038/s41598-021-95930-7
pii: 10.1038/s41598-021-95930-7
pmc: PMC8368064
doi:
Substances chimiques
Luminescent Proteins
0
enhanced green fluorescent protein
0
Green Fluorescent Proteins
147336-22-9
Cyclic AMP
E0399OZS9N
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Video-Audio Media
Langues
eng
Sous-ensembles de citation
IM
Pagination
16539Informations de copyright
© 2021. The Author(s).
Références
Sun, Y. C., Sun, X. F., Dyce, P. W., Shen, W. & Chen, H. The role of germ cell loss during primordial follicle assembly: A review of current advances. Int. J. Biol. Sci. 13, 449–457 (2017).
pubmed: 28529453
pmcid: 5436565
doi: 10.7150/ijbs.18836
Wenzel, M., Hamm, J. P., Peterka, D. S. & Yuste, R. Acute focal seizures start as local synchronizations of neuronal ensembles. J. Neurosci. 39, 8562–8575 (2019).
pubmed: 31427393
pmcid: 6807279
doi: 10.1523/JNEUROSCI.3176-18.2019
Goedert, M. & Spillantini, M. G. Propagation of Tau aggregates Tim Bliss. Mol. Brain 10, 18 (2017).
pubmed: 28558799
pmcid: 5450399
doi: 10.1186/s13041-017-0298-7
Paterlini-Brechot, P. & Benali, N. L. Circulating tumor cells (CTC) detection: Clinical impact and future directions. Cancer Lett. 253, 180–204 (2007).
pubmed: 17314005
doi: 10.1016/j.canlet.2006.12.014
Proserpio, V. & Lönnberg, T. Single-cell technologies are revolutionizing the approach to rare cells. Immunol. Cell Biol. 94, 225–229 (2016).
pubmed: 26620630
doi: 10.1038/icb.2015.106
McConnell, G. et al. A novel optical microscope for imaging large embryos and tissue volumes with sub-cellular resolution throughout. Elife 5, e18659 (2016).
pubmed: 27661778
pmcid: 5035146
doi: 10.7554/eLife.18659
McConnell, G. & Amos, W. B. Application of the Mesolens for subcellular resolution imaging of intact larval and whole adult Drosophila. J. Microsc. 270, 252–258 (2018).
pubmed: 29570774
pmcid: 5947746
doi: 10.1111/jmi.12693
Fan, J. et al. Video-rate imaging of biological dynamics at centimetre scale and micrometre resolution. Nat. Photonics 13, 809–816 (2019).
doi: 10.1038/s41566-019-0474-7
Lu, R. et al. Rapid mesoscale volumetric imaging of neural activity with synaptic resolution. Nat. Methods 17, 291–294 (2020).
pubmed: 32123393
pmcid: 7192636
doi: 10.1038/s41592-020-0760-9
Sofroniew, N. J., Flickinger, D., King, J. & Svoboda, K. A large field of view two-photon mesoscope with subcellular resolution for in vivo imaging. Elife 5, e14472 (2016).
pubmed: 27300105
pmcid: 4951199
doi: 10.7554/eLife.14472
Shaner, N. C. et al. Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nat. Biotechnol. 22, 1567–1572 (2004).
pubmed: 15558047
doi: 10.1038/nbt1037
Susaki, E. A. et al. Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis. Cell 157, 726–739 (2014).
pubmed: 24746791
doi: 10.1016/j.cell.2014.03.042
Seiriki, K. et al. Whole-brain block-face serial microscopy tomography at subcellular resolution using FAST. Nat. Protoc. 14, 1509–1529 (2019).
pubmed: 30962606
doi: 10.1038/s41596-019-0148-4
Nakamura, A. et al. Hoechst tagging: A modular strategy to design synthetic fluorescent probes for live-cell nucleus imaging. Chem. Commun. 50, 6149–6152 (2014).
doi: 10.1039/C4CC01753F
Stoker, M. G. P. & Rubin, H. Density dependent inhibition of cell growth in culture. Nature 215, 171–172 (1967).
pubmed: 6049107
doi: 10.1038/215171a0
Leontieva, O. V., Demidenko, Z. N. & Blagosklonny, M. V. Contact inhibition and high cell density deactivate the mammalian target of rapamycin pathway, thus suppressing the senescence program. Proc. Natl. Acad. Sci. U. S. A. 111, 8832–8837 (2014).
pubmed: 24889617
pmcid: 4066505
doi: 10.1073/pnas.1405723111
Apraiz, A., Mitxelena, J. & Zubiaga, A. Studying cell cycle-regulated gene expression by two complementary cell synchronization protocols. J. Vis. Exp. 2017, e55745 (2017).
Pozarowski, P. & Darzynkiewicz, Z. Analysis of cell cycle by flow cytometry. Methods Mol. Biol. 281, 301–311 (2004).
pubmed: 15220539
Sakaue-Sawano, A. et al. Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. Cell 132, 487–498 (2008).
pubmed: 18267078
doi: 10.1016/j.cell.2007.12.033
Puliafito, A. et al. Collective and single cell behavior in epithelial contact inhibition. Proc. Natl. Acad. Sci. U. S. A. 109, 739–744 (2012).
pubmed: 22228306
pmcid: 3271933
doi: 10.1073/pnas.1007809109
Wu, J. et al. Improved orange and red Ca
pubmed: 23452507
pmcid: 3689190
doi: 10.1021/cn400012b
Nagai, T., Yamada, S., Tominaga, T., Ichikawa, M. & Miyawaki, A. Expanded dynamic range of fluorescent indicators for Ca
pubmed: 15247428
pmcid: 490022
doi: 10.1073/pnas.0400417101
Barbini, P., Cevenini, G. & Massai, M. R. Nearest-neighbor analysis of spatial point patterns: Application to biomedical image interpretation. Comput. Biomed. Res. 29, 482–493 (1996).
pubmed: 9012570
doi: 10.1006/cbmr.1996.0035
Mikolajewicz, N., Mohammed, A., Morris, M. & Komarova, S. V. Mechanically stimulated ATP release from mammalian cells: Systematic review and meta-analysis. J. Cell Sci. 131, jcs223354 (2018).
pubmed: 30333142
doi: 10.1242/jcs.223354
Iyer, S. S. et al. Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc. Natl. Acad. Sci. U. S. A. 106, 20388–20393 (2009).
pubmed: 19918053
pmcid: 2787135
doi: 10.1073/pnas.0908698106
Weinbaum, S., Duan, Y., Thi, M. M. & You, L. An integrative review of mechanotransduction in endothelial, epithelial (renal) and dendritic cells (osteocytes). Cell. Mol. Bioeng. 4, 510–537 (2011).
pubmed: 23976901
doi: 10.1007/s12195-011-0179-6
Héja, L., Szabó, Z., Péter, M. & Kardos, J. Spontaneous Ca
doi: 10.3389/fncel.2021.617989
Gregor, T., Fujimoto, K., Masaki, N. & Sawai, S. The onset of collective behavior in social amoebae. Science 328, 1021–1025 (2010).
pubmed: 20413456
pmcid: 3120019
doi: 10.1126/science.1183415
Sawai, S., Thomason, P. A. & Cox, E. C. An autoregulatory circuit for long-range self-organization in Dictyostelium cell populations. Nature 433, 323–326 (2005).
pubmed: 15662425
doi: 10.1038/nature03228
Lee, K. J., Cox, E. C. & Goldstein, R. E. Competing patterns of signaling activity in Dictyostelium discoideum. Phys. Rev. Lett. 76, 1174–1177 (1996).
pubmed: 10061652
doi: 10.1103/PhysRevLett.76.1174
Levine, H., Aranson, I., Tsimring, L. & Truong, T. V. Positive genetic feedback governs cAMP spiral wave formation in Dictyostelium. Proc. Natl. Acad. Sci. U. S. A. 93, 6382–6386 (1996).
pubmed: 8692824
pmcid: 39031
doi: 10.1073/pnas.93.13.6382
Lauzeral, J., Halloy, J. & Goldbeter, A. Desynchronization of cells on the developmental path triggers the formation of spiral waves of cAMP during Dictyostelium aggregation. Proc. Natl. Acad. Sci. U. S. A. 94, 9153–9158 (1997).
pubmed: 9256451
pmcid: 23083
doi: 10.1073/pnas.94.17.9153
Grace, M. & Hütt, M.-T. Regulation of spatiotemporal patterns by biological variability: General principles and applications to Dictyostelium discoideum. PLOS Comput. Biol. 11, e1004367 (2015).
pubmed: 26562406
pmcid: 4643012
doi: 10.1371/journal.pcbi.1004367
Odaka, H., Arai, S., Inoue, T. & Kitaguchi, T. Genetically-encoded yellow fluorescent cAMP indicator with an expanded dynamic range for dual-color imaging. PLoS ONE 9, e100252 (2014).
pubmed: 24959857
pmcid: 4069001
doi: 10.1371/journal.pone.0100252
Fischer, M., Haase, I., Simmeth, E., Gerisch, G. & Müller-Taubenberger, A. A brilliant monomeric red fluorescent protein to visualize cytoskeleton dynamics in Dictyostelium. FEBS Lett. 577, 227–232 (2004).
pubmed: 15527790
doi: 10.1016/j.febslet.2004.09.084
Overholtzer, M. et al. A nonapoptotic cell death process, Entosis, that occurs by cell-in-cell invasion. Cell 131, 966–979 (2007).
pubmed: 18045538
doi: 10.1016/j.cell.2007.10.040
Mlynarczuk-Bialy, I. et al. Entosis: From cell biology to clinical cancer pathology. Cancers 12, 1–11 (2020).
doi: 10.3390/cancers12092481
Krishna, S. & Overholtzer, M. Mechanisms and consequences of entosis. Cell. Mol. Life Sci. 73, 2379–2386 (2016).
pubmed: 27048820
pmcid: 4889469
doi: 10.1007/s00018-016-2207-0
Saga, Y. & Yanagisawa, K. Macrocyst development in Dictyostelium discoideum. I. Induction of synchronous development by giant cells and biochemical analysis. J. Cell Sci. 55, 341–352 (1982).
pubmed: 6286696
doi: 10.1242/jcs.55.1.341
Tomosugi, W. et al. An ultramarine fluorescent protein with increased photostability and pH insensitivity. Nat. Methods 6, 351–353 (2009).
pubmed: 19349978
doi: 10.1038/nmeth.1317
Waddell, D. R. & Duffy, K. T. Breakdown of self/nonself recognition in cannibalistic strains of the predatory slime mold, Dictyostelium caveatum. J. Cell Biol. 102, 298–305 (1986).
pubmed: 3001102
doi: 10.1083/jcb.102.1.298
Nizak, C., Fitzhenry, R. J. & Kessin, R. H. Exploitation of other social amoebae by Dictyostelium caveatum. PLoS ONE 2, e212 (2007).
pubmed: 17299592
pmcid: 1790701
doi: 10.1371/journal.pone.0000212
Huang, S. Non-genetic heterogeneity of cells in development: more than just noise. Development 136, 3853–3862 (2009).
pubmed: 19906852
pmcid: 2778736
doi: 10.1242/dev.035139
Komin, N. & Skupin, A. How to address cellular heterogeneity by distribution biology. Curr. Opin. Syst. Biol. 3, 154–160 (2017).
doi: 10.1016/j.coisb.2017.05.010
Nitta, N. et al. Intelligent image-activated cell sorting. Cell 175, 266-276.e13 (2018).
pubmed: 30166209
doi: 10.1016/j.cell.2018.08.028
Ota, S. et al. Ghost cytometry. Science 360, 1246–1251 (2018).
pubmed: 29903975
doi: 10.1126/science.aan0096
Okamoto, K. et al. Single cell analysis reveals a biophysical aspect of collective cell-state transition in embryonic stem cell differentiation. Sci. Rep. 8, 1–13 (2018).
doi: 10.1038/s41598-018-30461-2
Chen, K. H., Boettiger, A. N., Moffitt, J. R., Wang, S. & Zhuang, X. Spatially resolved, highly multiplexed RNA profiling in single cells. Science 348, aaa6090 (2015).
pubmed: 25858977
pmcid: 4662681
doi: 10.1126/science.aaa6090
Ferreira-Martins, J. et al. Spontaneous calcium oscillations regulate human cardiac progenitor cell growth. Circ. Res. 105, 764–774 (2009).
pubmed: 19745162
pmcid: 2777616
doi: 10.1161/CIRCRESAHA.109.206698
Glaser, T. et al. ATP and spontaneous calcium oscillations control neural stem cell fate determination in Huntington’s disease: a novel approach for cell clock research. Mol. Psychiatry https://doi.org/10.1038/s41380-020-0717-5 (2020).
doi: 10.1038/s41380-020-0717-5
pubmed: 33328588
pmcid: 7738776
Kakizuka, T. et al. Cellular logics bringing the symmetry breaking in spiral nucleation revealed by trans-scale imaging. bioRxiv 2020.06.29.176891 (2020).
Challis, R. C. et al. Systemic AAV vectors for widespread and targeted gene delivery in rodents. Nat. Protoc. 14, 379–414 (2019).
pubmed: 30626963
doi: 10.1038/s41596-018-0097-3