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The Python and R codes used to process and analyse the Stereo-seq data are available on GitHub (https://github.com/Yuejiao2025/HESTA). These scripts orchestrate the use of established bioinformatics tools (for example, cell2location and scvi-tools) and are provided for reproducibility. They are not central to the conceptual conclusions of the paper.

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These authors contributed equally: Jiexue Pan, Yuejiao Li, Zhongliang Lin, Qing Lan, Ying Zhang, Huixi Chen, Shengwei Sui, Man Zhai, Gaochen Zhang

Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China

Jiexue Pan (潘洁雪), Shengwei Sui (隋盛威), Gaochen Zhang (张杲琛), Yi Cheng (程旖), Yunhui Tang (唐蕴慧), Qingchen Wang (王清晨), Yue Xu (徐越), Yiting Mao (毛翌婷), Xiaoying Yao (姚晓英), Xinmei Liu (刘欣梅), Congjian Xu (徐丛剑), Yanting Wu (吴琰婷), Chenming Xu (徐晨明), Hongbo Yang (杨红波), Guolian Ding (丁国莲) & Hefeng Huang (黄荷凤)

Shanghai Key Laboratory of Reproduction and Development, Shanghai, China

State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Shenzhen, China

Yuejiao Li (李月娇), Qing Lan (兰青), Ying Zhang (张颖), Man Zhai (翟曼), Chunyan Xu (许春燕), Haoqi Yan (严号棋), Xingxia Wang (王星霞), Hao Li (李昊), Yiping Zhu (朱依萍), Chang Wang (王畅), Tingyu Yang (杨听雨), Xuan Chen (陈璇), Qiuyu Qin (秦秋羽), Bin Jiang (江滨), Yuxing Ren (任玉杏), Yuxin Zhang (张雨昕), Minghui Yu (于明卉), Meiqi Luo (罗美琪), Ji Nancuo (南措吉), Fuhe Ma (马甫贺), Xin Jin (金鑫), Ya Gao (高雅) & Xun Xu (徐讯)

State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou, China

Yuejiao Li (李月娇), Qing Lan (兰青), Man Zhai (翟曼), Chunyan Xu (许春燕), Haoqi Yan (严号棋), Xingxia Wang (王星霞), Hao Li (李昊), Yiping Zhu (朱依萍), Chang Wang (王畅), Qiuyu Qin (秦秋羽), Bin Jiang (江滨), Yuxing Ren (任玉杏), Yuxin Zhang (张雨昕), Minghui Yu (于明卉), Lifang Wang (王丽芳), Yanrong Wei (卫彦蓉), Meiqi Luo (罗美琪), Fuhe Ma (马甫贺) & Ying Lei (雷莹)

BGI College & Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China

Key Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, China

Institute of Medical Genetics and Development, Zhejiang University, Hangzhou, China

Department of Obstetrics and Gynecology, Center for Reproductive Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, China

The International Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, China

College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Medical Technology College of Hebei Medical University, Shijiazhuang, China

Shenzhen Engineering Laboratory for Birth Defects Screening, Shenzhen, China

Shanxi Medical University — BGI Collaborative Center for Future Medicine, Shanxi Medical University, Taiyuan, China

Guangdong Provincial Key Laboratory of Genome Read and Write, Shenzhen, China

H.H. conceived the idea. H.H., X.X., G.D., Y. Gao, J.P., H. Yang and L.Z. made the study design. J.P., Y. Li, Y. Gao, G.D., H. Yang, X.X. and H.H. supervised the work. J.P. and G.D. designed the sample collection protocol. H.C., J.P., Z.L., Y.C., Y.T., X.Y., G.Z. and Y.X. collected the samples with the help of G.D., Q.C., Y. Guan, N.M., H. Lu, X. Li, T.Z. and Congjian Xu. Y. Gao, Y. Li, Z.L. and X.J. designed the spatial transcriptome experiments. Y. Li, Z.L., Q.L., J.P., M.Z., S.S., G.Z., H.C., Ying Zhang, Z.W., Z.O., F.M., Q.Q., B.J., Y.R., L.W., Y. Wei, J.N., Chunyan Xu, H. Yan, X.W., H. Li, Y. Zhu, C.W., T.Y., X.C., Yuxin Zhang, M.Y. and M.L. performed the bioinformatics analysis, statistical analysis and result visualization with the help of Y. Gao, J.P., G.D., X.J., H. Yang, Z.L., G.Z., Y.X., Y. Wei, Y.C., Y. Lei, J.S., H.H., X. Liu, Y. Wu and Chenming Xu. J.P., G.Z., Y.M. and G.D. conducted the ISH experiments. J.P., G.Z., Z.L. and G.L. performed the model organism validation experiments. Q.W. and H. Yang performed the zebrafish validation experiments. J.P., Y. Li, Z.L., Q.L., H.C., M.Z., G.Z. and S.S. wrote the first draft of the manuscript. J.P., Y. Gao, G.D., H.H., H. Yang, X.X., Z.L. and Y. Li revised and finalized the manuscript.

Correspondence to Lijian Zhao (赵立见), Hongbo Yang (杨红波), Ya Gao (高雅), Guolian Ding (丁国莲), Xun Xu (徐讯) or Hefeng Huang (黄荷凤).

None of the results in this study has been used for patent application. X.X. is the key inventor of DNBSEQ and Stereo-seq technologies covered in patents and patents applications, including ‘Array and method for detecting spatial information of nucleic acids’ (applicants: BGI Research and MGI Tech; inventors: A. Chen, X.X., J. Yang, L. Liu, O. Wang, Y. Li, S. Liao, G. Tang, Y. Jiang, C. Xu, M. Ni, W. Zhang, R. Drmanac and S. Drmanac; application numbers: CN202080036185.5 and RU2021135125), ‘Automatic control system of biochip and automatic control method thereof’ (applicant: BGI Research; inventors: Y. Hong, H. Kuang, Q. Yu, Q. Li, X. Sun, F. He, J. Xu, M. Shen, A. Chen, Y. Li, W. Zhang and X.X.; application number: PCT/CN2022/123075), ‘Biochip automatic control method and automatic control system thereof’ (applicant: BGI Research; inventors: F. He, X. Lei, A. Chen, Z. Qiu, Y. Hong, Z. Wan, M. Shen, A. Chen, Y. Li, W. Zhang and X.X.; application number: PCT/CN2022/123191), ‘Biochip and use and preparation method thereof’ (applicant: BGI Research; inventors: Y. Hong, Q. Li, A. Chen, Y. Li, W. Zhang and X.X.; application number: PCT/CN2022/123027), ‘Biochip container and methods for preparation and use thereof’ (applicant: BGI Research; inventors: Q. Yu, Y. Hong, Q. Li, A. Chen, Y. Li, W. Zhang and X.X.; application number: PCT/CN2022/127996), ‘Freezing and embedding device’ (applicants: BGI Research and BGI; inventors: J. Yi, L. Cui, S. Liao, A. Chen, W. Zhang and X.X.; application number: CN202223054698.4), ‘Methods, apparatus and applications for preparing candidate sequencing probe sets’ (applicant: MGI Tech; inventors: X.X., H. Jiang, C. Geng, G. Fan, E. Liang and Z. Zhu; application number: CN201610075006.4), and ‘Modified nucleoside or nucleotide’ (applicant: BGI Research; inventors: X.X., B. Teng, W. Zhang, A. Chen, H. Li, S. Yan, S. Zhuo, L. Shen, Y. Zhang, N. Gao, J. Zhao and S. Liao; application number: PCT/CN2021/125262). X.X. and L.Z. are employees of BGI Genomics, and hold stocks in BGI. Y. Li, Q.L., M.Z., Ying Zhang, Z.W., H. Yan, F.M., Q.Q., Y.R., B.J., L.W., J.N., Y. Wei, M.L., Chunyan Xu, X.W., H. Li, Y. Zhu, C.W., T.Y., X.C., Yuxin Zhang, M.Y., Z.O., Y. Lei, X.J. and Y. Gao are employees of BGI Research, and hold no intellectual property and commercial interests in DNBSEQ and Stereo-seq. J.P., Z.L., H.C., S.S., G.Z., Y.C., Y.T., Q.W., Y.X., G.L., Y.M., Q.C., Y. Guan, N.M., H. Lu, X. Li, T.Z., X.Y., X. Liu, J.S., Congjian Xu, Y. Wu, Chenming Xu, H. Yang, G.D. and H.H. declare no competing interests.

Nature thanks Konstantin Khodosevich, Malte Spielmann and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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a, Temporal progression of coding and non-coding transcripts in the main organs across CS12-23. b, The distribution and abundance of non-coding RNA subtypes in the main organs across CS12-23. lncRNA, long noncoding RNA; miRNA, microRNA; miscRNA, miscellaneous RNA; mt rRNA, mitochondrial ribosomal RNA; mt tRNA, mitochondrial transfer RNA; rRNA, ribosomal RNA; scaRNA, small cajal body-specific RNA; scRNA, small cytoplasmic RNA; snoRNA, small nucleolar RNA; snRNA, small nuclear RNA; sRNA, small non-coding RNA; vaultRNA, vault RNA. c, The GO terms of lncRNA predicted target genes in heart across CS12-23. NCC, neural crest cell; OFT, outflow tract; TGF, transforming growth factor. d, Violin plot showing the count number of genes/ the count number of UMIs/ percentage of mitochondria in each cell. e,f, Annotation of snRNA-seq data. e, UMAP of all cells colored by cell type for the annotation of snRNA-seq data. The inset dashed circle shows the same UMAP colored by developmental stage. f, Mapping of snRNA data to corresponding adjacent spatial transcriptomic data using Cell2location. Colors and numbers in e and f correspond to the 68 listed major cell cluster annotations.

Supplementary figures 1–7, legends for supplementary table and video files, and supplementary references

Heart rate of zebrafish in control, Shox2, Roraa, Rorab, Elapor2b and Vsnl1b knockdown group

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