Programming self-organizing multicellular structures with synthetic cell-cell signaling
Open accessAbstract
Engineering multilayered cellular structures: The ability to program the manufacture of biological structures may yield new biomaterials or synthetic tissues and organs. Toda et al. engineered mammalian “sender” and “receiver” cells with synthetic cell surface ligands and receptors that controlled gene regulatory circuits based on Notch signaling. Programming the cells to express cell adhesion molecules and other regulatory molecules enabled spontaneous formation of multilayered structures, like those that form during embryonic development. The three-layered structures even showed regeneration after injury. Science , this issue p. 156
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.
Integrity signals
Registry
Cites
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.
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?
Laboratory experiments and engineered multicellular systems suggest that simple MC10 is relatively easy to obtain.
“Laboratory experiments [178,179] and engineered multicellular systems [180,181] suggest that simple MC10 is relatively easy to obtain.”
From Fundamental constraints to the logic of living systems (2024) · cites this paper as [181]
The section “Synthetic assembly is robust, reversible, and self-repairing” reports that an engineered three-layer structure formed in about 90% of cultures. The paper therefore supports the claim that simple multicellular organization can be produced reliably in an engineered system, but it does not identify the result as “MC10” or establish how readily that specific level is obtained. (LLM, conf=0.83)
Experimental — accuracy not yet measured
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
The chemical basis of morphogenesis
Turing, A. M. (1952) · Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences · doi:10.1098/rstb.1952.0012 · Cited by 11,733 · see citing works
Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia
Grupp, S. A., Kalos, M., Barrett, D., Aplenc, R., Porter, D. L., Rheingold, S. R., Teachey, D. T., Chew, A., Hauck, B., Wright, J. F., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1215134 · Cited by 3,509 · see citing works
Positional information and the spatial pattern of cellular differentiation
Wolpert, L. (1969) · Journal of Theoretical Biology · doi:10.1016/s0022-5193(69)80016-0 · Cited by 3,091 · see citing works
Programmed Cell Death in Animal Development
Jacobson, M. D., Weil, M., & RAFF, M. C. (1997) · Cell · doi:10.1016/s0092-8674(00)81873-5 · Cited by 2,685 · see citing works
Notch signalling: a simple pathway becomes complex
Bray, S. J. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2009 · Cited by 2,620 · see citing works
Chromatin modification and epigenetic reprogramming in mammalian development
Li, E. (2002) · Nature Reviews Genetics · doi:10.1038/nrg887 · Cited by 1,900 · see citing works
Programmable self-assembly in a thousand-robot swarm
Rubenstein, M., Cornejo, A., & Nagpal, R. (2014) · Science · doi:10.1126/science.1254295 · Cited by 1,266 · see citing works
A synthetic multicellular system for programmed pattern formation
Basu, S., Gerchman, Y., Collins, C. H., Arnold, F. H., & Weiss, R. (2005) · Nature · doi:10.1038/nature03461 · Cited by 1,158 · see citing works
The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans
King, N., Westbrook, M. J., Young, S. L., Kuo, A., Abedin, M., Chapman, J., Fairclough, S., Hellsten, U., Isogai, Y., Letunic, I., et al. (2008) · Nature · doi:10.1038/nature06617 · Cited by 1,139 · see citing works
Self-citationVinci, M., Gowan, S., Boxall, F., Patterson, L., Zimmermann, M., Court, W., Lomas, C., Mendiola, M., Hardisson, D., & Eccles, S. A. (2012) · BMC Biology · doi:10.1186/1741-7007-10-29 · Cited by 1,024 · see citing works
Engineering Customized Cell Sensing and Response Behaviors Using Synthetic Notch Receptors
Morsut, L., Roybal, K. T., Xiong, X., Gordley, R. M., Coyle, S. M., Thomson, M., & Lim, W. A. (2016) · Cell · doi:10.1016/j.cell.2016.01.012 · Cited by 1,002 · see citing works
Self-citationThe differential adhesion hypothesis: a direct evaluation
Foty, R. A., & Steinberg, M. S. (2005) · Developmental Biology · doi:10.1016/j.ydbio.2004.11.012 · Cited by 908 · see citing works
Expressed recombinant cadherins mediate cell sorting in model systems
Nose, A., Nagafuchi, A., & Takeichi, M. (1988) · Cell · doi:10.1016/0092-8674(88)90114-6 · Cited by 672 · see citing works
Tissue biology perspective on macrophages
Okabe, Y., & Medzhitov, R. M. (2015) · Nature Immunology · doi:10.1038/ni.3320 · Cited by 633 · see citing works
Collier, J. R., Monk, N., Maini, P. K., et al. (1996) · Journal of Theoretical Biology · doi:10.1006/jtbi.1996.0233 · Cited by 533 · see citing works
A robust pipeline for rapid production of versatile nanobody repertoires
Fridy, P. C., Li, Y., Keegan, S., Thompson, M. K., Nudelman, I., Scheid, J. F., Oeffinger, M., Nussenzweig, M. C., Fenyö, D., Chait, B. T., et al. (2014) · Nature Methods · doi:10.1038/nmeth.3170 · Cited by 493 · see citing works
Bridging the regeneration gap: Genetic insights from diverse animal models
Alvarado, A. S., & Tsonis, P. A. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1923 · Cited by 467 · see citing works
van den Brink, S., Baillie‐Johnson, P., Balayo, T., Hadjantonakis, A., Nowotschin, S., Turner, D. A., & Arias, A. M. (2014) · Development · doi:10.1242/dev.113001 · Cited by 461 · see citing works
Collective cell migration in development
Scarpa, E., & Mayor, R. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201508047 · Cited by 459 · see citing works
Positional information and reaction-diffusion: two big ideas in developmental biology combine
Green, J. B. A., & Sharpe, J. A. (2015) · Development · doi:10.1242/dev.114991 · Cited by 430 · see citing works
Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro
Harrison, S., Sözen, B., Christodoulou, N., Kyprianou, C., & Zernicka‐Goetz, M. (2017) · Science · doi:10.1126/science.aal1810 · Cited by 393 · see citing works
Cadherin-mediated cell adhesion and tissue segregation: qualitative and quantitative determinants
Duguay, D., Foty, R. A., & Steinberg, M. S. (2003) · Developmental Biology · doi:10.1016/s0012-1606(02)00016-7 · Cited by 389 · see citing works
Lineage specification in the mouse preimplantation embryo
Chazaud, C., & Yamanaka, Y. (2016) · Development · doi:10.1242/dev.128314 · Cited by 317 · see citing works
From morphogen to morphogenesis and back
Gilmour, D. T., Rembold, M., & Leptin, M. (2017) · Nature · doi:10.1038/nature21348 · Cited by 311 · see citing works
Alegado, R. A., Brown, L. W., Cao, S., Dermenjian, R. K., Zuzow, R., Fairclough, S. R., Clardy, J., & King, N. (2012) · eLife · doi:10.7554/elife.00013 · Cited by 249 · see citing works
The Premetazoan Ancestry of Cadherins
Sigg, M. A., & King, N. (2008) · Science · doi:10.1126/science.1151084 · Cited by 239 · see citing works
Elowitz, M. B., & Lim, W. A. (2010) · Nature · doi:10.1038/468889a · Cited by 216 · see citing works
Self-citationNewman, S. A., & Bhat, R. (2009) · The International Journal of Developmental Biology · doi:10.1387/ijdb.072481sn · Cited by 208 · see citing works
Origin of metazoan cadherin diversity and the antiquity of the classical cadherin/β-catenin complex
Nichols, S., Roberts, B., Richter, D. J., Fairclough, S. R., & King, N. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1120685109 · Cited by 193 · see citing works
Bacterial lipids activate, synergize, and inhibit a developmental switch in choanoflagellates
Woznica, A., Cantley, A. M., Beemelmanns, C., Freinkman, E., Clardy, J., & King, N. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1605015113 · Cited by 136 · see citing works
A self-organization framework for symmetry breaking in the mammalian embryo
Wennekamp, S., Mesecke, S., Nédélec, F., & Hiiragi, T. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3602 · Cited by 115 · see citing works
Using synthetic biology to explore principles of development
Davies, J. A. (2017) · Development · doi:10.1242/dev.144196 · Cited by 112 · see citing works
Paradoxical Signaling by a Secreted Molecule Leads to Homeostasis of Cell Levels
Hart, Y., Reich-Zeliger, S., Antebi, Y. E., Zaretsky, I., Mayo, A., Alon, U. S., & Friedman, N. (2014) · Cell · doi:10.1016/j.cell.2014.07.033 · Cited by 106 · see citing works
Cachat, É., Liu, W., Martin, K., Yuan, X., Yin, H., Hohenstein, P., & Davies, J. A. (2016) · Scientific Reports · doi:10.1038/srep20664 · Cited by 96 · see citing works
Synthetic lateral inhibition governs cell-type bifurcation with robust ratios
Matsuda, M., Koga, M., Woltjen, K., et al. (2015) · Nature Communications · doi:10.1038/ncomms7195 · Cited by 92 · see citing works
Synthetic morphology: prospects for engineered, self‐constructing anatomies
Davies, J. A. (2008) · Journal of Anatomy · doi:10.1111/j.1469-7580.2008.00896.x · Cited by 91 · see citing works
Structural and energetic determinants of adhesive binding specificity in type I cadherins
Vendôme, J., Felsövályi, K., Song, H., Yang, Z., Jin, X., Brasch, J., Harrison, O. J., Ahlsén, G., Bahna, F. A., Kaczynska, A., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1416737111 · Cited by 90 · see citing works
Synthetic MorphogenesisPreprint
Teague, B. P., Guye, P., & Weiss, R. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a023929 · Cited by 90 · see citing works
Specification and Simulation of Synthetic Multicelled Behaviors
Jang, S.-H., Oishi, K., Egbert, R. G., & Klavins, E. (2012) · ACS Synthetic Biology · doi:10.1021/sb300034m · Cited by 73 · see citing works
An operational view of intercellular signaling pathways
Antebi, Y. E., Nandagopal, N., & Elowitz, M. B. (2017) · Current Opinion in Systems Biology · doi:10.1016/j.coisb.2016.12.003 · Cited by 62 · see citing works
Microfluidic guillotine for single-cell wound repair studies
Blauch, L. R., Gai, Y., Khor, J. W., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705059114 · Cited by 41 · see citing works
Self-citationCreating to understand – developmental biology meets engineering in Paris
Kicheva, A., & Rivron, N. C. (2017) · Development · doi:10.1242/dev.144915 · Cited by 12 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [26]Turing AM, Philos. Trans. R. Soc. London Ser. B 237, 37– 72 (1952).
Cited by
Sorted by citations
Progress and potential in organoid research
Rossi, G., Manfrin, A., & Lutolf, M. P. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0051-9 · Cited by 1,182 · see citing works
Hofer, M., & Lutolf, M. P. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00279-y · Cited by 1,184 · see citing works
Takebe, T., & Wells, J. M. (2019) · Science · doi:10.1126/science.aaw7567 · Cited by 417 · see citing works
Cell-cell communication: New insights and clinical implications
Su, J., Song, Y., Zhu, Z., Huang, X., Fan, J., Qiao, J., & Mao, F. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01888-z · Cited by 433 · see citing works
A cellular platform for the development of synthetic living machines
Blackiston, D., Lederer, E., Kriegman, S., Garnier, S., Bongard, J., & Levin, M. (2021) · Science Robotics · doi:10.1126/scirobotics.abf1571 · Cited by 178 · see citing works
Statistical and machine learning methods for spatially resolved transcriptomics data analysis
Zeng, Z., Li, Y., Li, Y., & Luo, Y. (2022) · Genome Biology · doi:10.1186/s13059-022-02653-7 · Cited by 186 · see citing works
The Cellular Immunotherapy Revolution: Arming the Immune System for Precision Therapy
Paucek, R. D., Baltimore, D., & Li, G. (2019) · Trends in Immunology · doi:10.1016/j.it.2019.02.002 · Cited by 104 · see citing works
Fundamental constraints to the logic of living systems
Solé, R., Kempes, C. P., Corominas-Murtra, B., De Domenico, M., Kolchinsky, A., Lachmann, M., Libby, E., Saavedra, S., Smith, E., & Wolpert, D. (2024) · Interface Focus · doi:10.1098/rsfs.2024.0010 · Cited by 34 · see citing works
- Authors
- Toda, S., Blauch, L. R., Tang, S. K. Y., Morsut, L., & Lim, W. A.
- Affiliations
- Howard Hughes Medical Institute (US)
- Stanford University (US)
- University of Southern California (US)
- Corresponding author
- Morsut, Leonardo
- Lim, Wendell A.
- Venue
- Science
- Published
- 2018-07-13
- Volume
- 361
- Issue
- 6398
- Pages
- 156-162
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC6492944
- OpenAlex
- W2806766210
- Cited by
- 470
- References
- 42
- Citations by year
- 2026: 37 · 2025: 50 · 2024: 70 · 2023: 52 · 2022: 63 · 2021: 65 · 2020: 70 · 2019: 45 · 2018: 18
- FWCI
- 17.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Science Foundation (DBI-1548297)
- National Institutes of Health (5P50GM081879, 1K99EB021030)
- Howard Hughes Medical Institute
- Defense Sciences Office, DARPA
- Human Frontier Science Program
- Japan Society for the Promotion of Science
- European Molecular Biology Organization
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- self-organization, multicellular structures, cell-to-cell communication, juxtacrine signaling, cell sorting, symmetry breaking, tissue regeneration, evolution of multicellularity, synthetic gene circuits, tissue engineering
- MeSH terms
- Cell Adhesion, Cell Communication, Cells, Morphogenesis, Signal Transduction, Spheroids, Cellular, Artificial Cells, Cell Engineering
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