Whole-embryo spatial transcriptomics at subcellular resolution from gastrulation to organogenesis

• 成果类型: Article
• 署名作者: Wan, Yinan; El Kholtei, Jakob; Jenie, Ignatius; Colomer-Rosell, Mariona; Liu, Jialin; Zhang, Qinghua; Acedo, Joaquin Navajas; Du, Lucia Y.; Codina-Tobias, Mireia; Wang, Mengfan; Zheng, Wei; Lin, Edward; Chuang, Tzy-Harn; Mayseless, Oded; Sawh, Ahilya; Mango, Susan E.; Yu, Guoqiang; Bintu, Bogdan; Schier, Alexander F.
• 署名单位: University of Basel; University of California System; University of California San Diego; Tsinghua University; Virginia Polytechnic Institute & State University; University of Toronto
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adt3439
• 发表日期: 2026-03-12
• 页码: eadt3439
• 关键词: in-situ hybridization; cell lineages; tissue; reconstruction; expression; biology; enhancers; atlas; axis; rnas

摘要

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.