Resolving the gene expression maps of human first-trimester chorionic villi with spatial transcriptome.

Area of Science:

• Reproductive Biology
• Genomics
• Developmental Biology

Background:

• The placenta is vital for mammalian fetal development.
• Spatial transcriptomic profiling offers insights into placental structure and function.

Purpose of the Study:

• To map the spatial transcriptome of first-trimester human placental villi.
• To identify cell types, communication, and regulatory pathways within the placenta.

Main Methods:

• Modified Stereo-seq applied to paraformaldehyde (PFA)-fixed human placental villi.
• Identification of major cell types (SCT, VCT, FB, EVT) via spatial transcriptomics.
• Deconvolution of scRNA-seq data to locate minor cell types (HB, Endo).

Main Results:

• PFA fixation improved tissue morphology and RNA signal specificity compared to fresh tissue.
• Identified ligand-receptor interactions promoting syncytiotrophoblast differentiation.
• Revealed spatial localization of regulons linked to hormone transport, cell cycle, and nutrient pathways in SCT.
• Characterized EVT pathways including epithelial-mesenchymal transition and ECM organization.
• Identified viral receptors and drug transporters, offering insights into disease transmission and drug metabolism.

Conclusions:

• Spatial transcriptomics of human villi enables sophisticated analyses like cell communication and regulatory activity.
• The study provides a valuable spatial resource for investigating placental development, physiology, and pathology.
• Findings contribute to understanding vertical transmission of infectious diseases and drug metabolism.