2. Academic Validation
  3. A spatiotemporal transcriptomic atlas of mouse placentation

A spatiotemporal transcriptomic atlas of mouse placentation

  • Cell Discov. 2024 Oct 22;10(1):110. doi: 10.1038/s41421-024-00740-6.
Yanting Wu # 1 2 3 4,  Kaizhen Su # 5 6 7,  Ying Zhang # 8 9,  Langchao Liang # 10 11,  Fei Wang 8,  Siyue Chen 12,  Ling Gao 12,  Qiutong Zheng 12,  Cheng Li 12,  Yunfei Su 12,  Yiting Mao 12,  Simeng Zhu 13,  Chaochao Chai 10 11,  Qing Lan 8,  Man Zhai 8,  Xin Jin 8,  Jinglan Zhang 12 14 15,  Xun Xu 8 16,  Yu Zhang 17,  Ya Gao 18 19 20,  Hefeng Huang 21 22 23 24 25 26
Affiliations

Affiliations

  • 1 Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China. yanting_wu@163.com.
  • 2 Key Laboratory of Reproductive Genetics (Ministry of Education), Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. yanting_wu@163.com.
  • 3 Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences (No. 2019RU056), Shanghai, China. yanting_wu@163.com.
  • 4 Shanghai Key Laboratory of Reproduction and Development, Shanghai, China. yanting_wu@163.com.
  • 5 Key Laboratory of Reproductive Genetics (Ministry of Education), Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 6 Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 7 International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • 8 BGI Research, Shenzhen, Guangdong, China.
  • 9 Shanxi Medical University - BGI Collaborative Center for Future Medicine, Shanxi Medical University, Taiyuan, Shanxi, China.
  • 10 BGI Research, Qingdao, Shandong, China.
  • 11 College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • 12 Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China.
  • 13 Department of Cardiology, Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 14 Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences (No. 2019RU056), Shanghai, China.
  • 15 Shanghai Key Laboratory of Reproduction and Development, Shanghai, China.
  • 16 Guangdong Provincial Key Laboratory of Genome Read and Write, Shenzhen, Guangdong, China.
  • 17 Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China. zhang_yu_sfy@fudan.edu.cn.
  • 18 BGI Research, Shenzhen, Guangdong, China. gaoya@genomics.cn.
  • 19 Shanxi Medical University - BGI Collaborative Center for Future Medicine, Shanxi Medical University, Taiyuan, Shanxi, China. gaoya@genomics.cn.
  • 20 Shenzhen Engineering Laboratory for Birth Defects Screening, BGI Research, Shenzhen, Guangdong, China. gaoya@genomics.cn.
  • 21 Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China. huanghefg@hotmail.com.
  • 22 Key Laboratory of Reproductive Genetics (Ministry of Education), Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. huanghefg@hotmail.com.
  • 23 Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences (No. 2019RU056), Shanghai, China. huanghefg@hotmail.com.
  • 24 Shanghai Key Laboratory of Reproduction and Development, Shanghai, China. huanghefg@hotmail.com.
  • 25 Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. huanghefg@hotmail.com.
  • 26 International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. huanghefg@hotmail.com.
  • # Contributed equally.
PMID: 39438452 DOI: 10.1038/s41421-024-00740-6
Abstract

The placenta, a temporary but essential organ for gestational support, undergoes intricate morphological and functional transformations throughout gestation. However, the spatiotemporal patterns of gene expression underlying placentation remain poorly understood. Utilizing Stereo-seq, we constructed a Mouse Placentation Spatiotemporal Transcriptomic Atlas (MPSTA) spanning from embryonic day (E) 7.5 to E14.5, which includes the transcriptomes of large trophoblast cells that were not captured in previous single-cell atlases. We defined four distinct strata of the ectoplacental cone, an early heterogeneous trophectoderm structure, and elucidated the spatial trajectory of trophoblast differentiation during early postimplantation stages before E9.5. Focusing on the labyrinth region, the interface of nutrient exchange in the mouse placenta, our spatiotemporal ligand-receptor interaction analysis unveiled pivotal modulators essential for trophoblast development and placental angiogenesis. We also found that paternally expressed genes are exclusively enriched in the placenta rather than in the decidual regions, including a cluster of genes enriched in endothelial cells that may function in placental angiogenesis. At the invasion front, we identified interface-specific transcription factor regulons, such as Atf3, Jun, Junb, STAT6, Mxd1, Maff, Fos, and Irf7, involved in gestational maintenance. Additionally, we revealed that maternal high-fat diet exposure preferentially affects this interface, exacerbating inflammatory responses and disrupting angiogenic homeostasis. Collectively, our findings furnish a comprehensive, spatially resolved atlas that offers valuable insights and benchmarks for future explorations into placental morphogenesis and pathology.

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