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<p>The mechanism underlying the establishment of human endometrial receptivity remains elusive, constituting a significant obstacle to advancing our knowledge of female infertility. Via integrating high-resolution spatiotemporal and single-cell transcriptomic profiling and in situ sequencing, we construct a spatiotemporal atlas of human endometrial receptivity at single-cell resolution. Our study depicts detailed spatial molecular topography governing the opening and closing of human endometrial receptivity. Notably, the results indicate that stromal-specific <i>NR2F1</i>, <i>CEBPD</i> and epithelial-specific <i>SGK1</i>, <i>KLF5</i> and <i>ELF3</i> are closely associated with the opening of implantation window. Furthermore, cholesterol metabolism is found to promote ciliogenesis. Remarkably, we identify stroma- and epithelium-specific factors and unravel a previously unappreciated role of FGFs-FGFR2 signaling pathway mediating stroma-epithelium crosstalk in epithelial differentiation during the onset of receptivity. This spatiotemporally resolved receptivity code provides insights into the female fertility, with potential implications for the intervention of female infertility.</p>

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Decrypting spatiotemporal code of human endometrial receptivity

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月21日

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  • Yang Liu,
  • Yang Wang,
  • Leilei Zhang,
  • Yedong Tang,
  • Yetao Hong,
  • Meng Liu,
  • Mengyuan Wang,
  • Ya Sun,
  • Xiaoyue Shen,
  • Jie Mei,
  • Min Wu,
  • Na Kong,
  • Shuangbo Kong,
  • Haili Bao,
  • Wenbo Deng,
  • Guijun Yan,
  • Haibin Wang,
  • Haixiang Sun

摘要

The mechanism underlying the establishment of human endometrial receptivity remains elusive, constituting a significant obstacle to advancing our knowledge of female infertility. Via integrating high-resolution spatiotemporal and single-cell transcriptomic profiling and in situ sequencing, we construct a spatiotemporal atlas of human endometrial receptivity at single-cell resolution. Our study depicts detailed spatial molecular topography governing the opening and closing of human endometrial receptivity. Notably, the results indicate that stromal-specific NR2F1, CEBPD and epithelial-specific SGK1, KLF5 and ELF3 are closely associated with the opening of implantation window. Furthermore, cholesterol metabolism is found to promote ciliogenesis. Remarkably, we identify stroma- and epithelium-specific factors and unravel a previously unappreciated role of FGFs-FGFR2 signaling pathway mediating stroma-epithelium crosstalk in epithelial differentiation during the onset of receptivity. This spatiotemporally resolved receptivity code provides insights into the female fertility, with potential implications for the intervention of female infertility.