2. Academic Validation
  3. A single-cell time-series atlas of endothelial cell embryonic development

A single-cell time-series atlas of endothelial cell embryonic development

  • Cell. 2026 Mar 5;189(5):1573-1590.e24. doi: 10.1016/j.cell.2026.01.002.
Lihui Lin 1,  Jing Zhong 1,  Fuqing Jiang 2,  Yu-Xiang Wang 1,  Lan-Yue Ma 2,  Jia-Xin Yang 3,  Yu-Yan Li 2,  Rong-Rong Gao 2,  Huijian Feng 2,  Baomei Cai 4,  Ziyu Feng 4,  Xin Zhou 2,  Ya-Hai Shu 5,  Pan Chen 1,  Xue Wu 6,  Chen-Leng Cai 5,  Qiang Wang 3,  Guangming Wu 4,  Duanqing Pei 7,  Shangtao Cao 8,  Yang Liu 9,  Guangdun Peng 10,  Jiekai Chen 11,  Qi Chen 12
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 511436, China.
  • 2 Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 511436, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 3 The Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of Technology, Guangzhou 510006, China.
  • 4 Guangzhou National Laboratory, Guangzhou 510005, China.
  • 5 Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
  • 6 Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 7 Laboratory of Cell Fate Control, School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang, China. Electronic address: [email protected].
  • 8 Guangzhou National Laboratory, Guangzhou 510005, China. Electronic address: [email protected].
  • 9 The Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of Technology, Guangzhou 510006, China. Electronic address: [email protected].
  • 10 Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 511436, China. Electronic address: [email protected].
  • 11 Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 511436, China. Electronic address: [email protected].
  • 12 Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 511436, China. Electronic address: [email protected].
PMID: 41702400 DOI: 10.1016/j.cell.2026.01.002
Abstract

Endothelial cells (ECs) are essential components of the vertebrate circulatory system; however, a comprehensive atlas characterizing how ECs acquire organ-specific transcriptomic heterogeneity has not been established. Here, we generated a time-series endothelial resource covering the entirety of mouse embryonic development, including 26 time points and 8 organs. Time-series multi-organ comparison revealed emergence timing and lineage trajectory of organotypic ECs together with organ-specific genes and pathways. Using these resources, we found that most ECs showed distinguishable organ specificity before late gestation. The organotypic EC-enriched genes were associated with vascular function in the organs. Human and mouse pulmonary ECs underwent an evolutionarily conserved transcriptional transition. Endothelial-specific knockout of Casz1, a pulmonary EC-enriched transcription factor, resulted in impaired vascular growth, disturbed pulmonary endothelial organotypic differentiation, and deficient epithelial-EC crosstalk. Our work provides a powerful endothelial resource that reveals fundamental principles of organ-specific EC differentiation and uncovers previously unknown molecular mechanisms governing lung-specific vascular development.

Keywords

Casz1; angiogenesis; embryonic development; endothelial cells; interorgan comparison; lung development; organ-specific differentiation; organotypic vessel; single-cell atlas; vascular development.

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