Whole-embryo spatial transcriptomics at subcellular resolution from gastrulation to organogenesis
Gene expression patterns underlie development, but their systematic detection in whole embryos has remained elusive. We introduce a whole-embryo imaging platform using multiplexed error-robust fluorescent in situ hybridization (weMERFISH). We quantified the expression of 495 genes in zebrafish embryos at subcellular resolution and generated an online atlas detailing the expression of 25,872 genes and accessibility of 294,954 chromatin regions during embryogenesis. Expression patterns often corresponded to composites of tissue-specific accessible elements, and expression changes aligned with cellular maturation and morphogenesis. Integration with live imaging revealed how similar expression patterns can emerge through different dynamics and showed that sharp boundaries develop through changes in gene expression rather than through cell sorting. These results establish multiplexed whole-embryo spatial transcriptomics and reveal the regulation and dynamics of embryonic gene expression patterns.
Authors
- Lucia Y. Du (ORCID: https://orcid.org/0000-0003-0151-3783)
- Jakob El Kholtei (ORCID: https://orcid.org/0000-0002-1734-7188)
- Bogdan Bintu (ORCID: https://orcid.org/0000-0001-9096-5858)
- Ahilya N. Sawh (ORCID: https://orcid.org/0000-0001-9494-6654)
- Joaquín Navajas Acedo (ORCID: https://orcid.org/0000-0003-2855-6660)
- Mariona Colomer-Rosell (ORCID: https://orcid.org/0000-0002-3523-315X)
- Oded Mayseless (ORCID: https://orcid.org/0000-0002-9556-8541)
- Alexander F. Schier (ORCID: https://orcid.org/0000-0001-7645-5325)
- G. Yu
- Susan E. Mango (ORCID: https://orcid.org/0000-0002-2146-3237)
- Jialin Liu (ORCID: https://orcid.org/0000-0002-9883-0963)
- Mengfan Wang
- Wei Zheng (ORCID: https://orcid.org/0009-0006-6662-0191)
- Ignatius Jenie (ORCID: https://orcid.org/0009-0009-2849-1116)
- Edward Lin
- Tzy-Harn Chuang
- Qinghua Zhang
- Yinan Wan
- Mireia Codina-Tobias
Institutions
- University of Basel (CH)
- University of Toronto (CA)
- University of California San Diego (US)
- Allen Institute (US)
- Virginia Tech (US)
- Tsinghua University (CN)
Publication Details
- Journal
- Science
- Published
- 2026-03-12
- DOI
- https://doi.org/10.1126/science.adt3439
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.00