Academic Journal
Single-cell spatial mapping reveals reproducible cell type organization and spatially dependent gene expression in gastruloids.
| Τίτλος: | Single-cell spatial mapping reveals reproducible cell type organization and spatially dependent gene expression in gastruloids. |
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| Συγγραφείς: | Triandafillou C; Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, United States., Sompalle P; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, United States.; Department of Physics and Astronomy, School of Arts and Sciences, University of Pennsylvania, Philadelphia, United States., Heyman Y; Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, United States., Raj A; Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, United States.; Genetics and Epigenetics, Cell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States. |
| Πηγή: | ELife [Elife] 2026 Sep 29; Vol. 15. Date of Electronic Publication: 2026 Sep 29. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012- |
| Ιατρικοί όροι (MeSH): | Gastrula*/cytology , Single-Cell Analysis* , Gene Expression Regulation, Developmental* , Gastrulation*, Animals ; Single-Cell Gene Expression Analysis ; Cell Differentiation ; Spatial Transcriptomics ; Gene Expression Profiling |
| Περίληψη: | Gastruloids are stem-cell-based models that recapitulate key aspects of mammalian gastrulation, including the formation of an anterior-posterior axis. However, we do not have detailed spatial information about gene expression and cell type organization, particularly at the level of individual gastruloids. Here, we report a spatially resolved, single-cell molecular catalog of the transcriptomes of 26 individual gastruloids. We found that cell type composition and tissue-scale spatial organization were largely consistent across gastruloids, but meso-scale patterning of specific cell types varied between samples. Posterior cell types formed distinct, organized clusters, while anterior cell types were more disorganized. To distinguish progressive differentiation from cell type differences, we developed the L-score, a parameter-free quantification of mutually exclusive gene expression. This analysis revealed spatial organization without explicit encoding, recapitulated known cell type relationships, and identified novel gene expression states and spatial subclusters within cell types. We confirmed that in gastruloids, neuromesodermal precursor differentiation occurred through a continuous, spatially coordinated process. We also showed that endothelial precursors exhibited unique spatial organization and had distinct gene expression profiles dependent on their association with anterior somitic or posterior endodermal tissues. This work enables the rigorous use of gastruloids as models for studying the molecular mechanisms underlying mammalian development and tissue organization and introduces new computational tools for analyzing spatially resolved single-cell datasets. (© 2026, Triandafillou et al.) |
| Competing Interests: | CT, PS, YH No competing interests declared, AR A.R. receives royalties related to Stellaris RNA FISH probes. A.R. is a scientific advisory board member, consultant and/or co-founder of Spatial Genomics, Cytopixel Software, and Cellular Intelligence |
| Σχόλια: | Update of: bioRxiv. 2025 Jul 31:2025.07.14.664617. doi: 10.1101/2025.07.14.664617.. (PMID: 40766620) |
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| Grant Information: | DRG-2465-22 United States DRCRF Damon Runyon Cancer Research Foundation; Grant 63532 The John Templeton Foundation |
| Contributed Indexing: | Keywords: computational biology; developmental biology; gastrulation; gastruloids; mouse; organoid model; spatial transcriptomics; systems biology |
| Entry Date(s): | Date Created: 20260929 Date Completed: 20260929 Latest Revision: 20261001 |
| Update Code: | 20261001 |
| PubMed Central ID: | PMC13623378 |
| DOI: | 10.7554/eLife.109268 |
| PMID: | 42808695 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2050-084X |
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| DOI: | 10.7554/eLife.109268 |