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Comparative Single-Cell Transcriptomic Atlas Reveals the Genetic Regulation of Reproductive Traits.

Bingru Zhao1, Hanpeng Luo2, Dailu Guan3

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Summary

This study created a sheep and human cell atlas to understand fertility. Conserved cell types and signaling pathways were identified, offering insights into reproduction and complex traits.

Keywords:
GWAS integrationcross‐species comparisonsevolutionary conservationreproductive biologysingle‐cell transcriptomics

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Area of Science:

  • Comparative genomics
  • Reproductive biology
  • Neuroendocrinology

Background:

  • Reproduction relies on intricate neuroendocrine and reproductive systems.
  • Understanding conserved fertility mechanisms requires cross-species analysis.

Purpose of the Study:

  • To construct a high-resolution single-cell transcriptomic atlas of sheep reproductive and CNS tissues.
  • To integrate this atlas with human datasets for comparative analysis.
  • To identify conserved cellular programs and signaling pathways regulating fertility.

Main Methods:

  • Single-cell RNA sequencing of 15 sheep tissues and integration with 13 human tissue datasets.
  • Orthologous gene analysis to identify shared cell types and transcriptional programs.
  • Genome-wide association studies (GWAS) integration to pinpoint fertility-associated genes.
  • Cell-cell communication analysis to elucidate signaling pathways.

Main Results:

  • A comparative atlas of over 1.09 million cells, identifying 76 major cell types.
  • High conservation (71.1%) of cell types and regulatory networks between sheep and humans.
  • Identification of UNC5-SLIT-BMP signaling cascades in neuroendocrine fertility regulation.
  • Validation of conserved cell types in recapitulating human GWAS associations for complex traits.

Conclusions:

  • The cross-species atlas reveals conserved mechanisms in fertility regulation.
  • Identified signaling pathways provide targets for understanding and improving fertility.
  • This resource aids research into conserved cellular programs and inter-organ signaling for complex traits.