A single-cell and spatial atlas of early human olfactory development

Area of Science:

• Developmental Biology
• Neuroscience
• Genomics

Background:

• Early human nasal development is poorly understood due to tissue access limitations.
• The nasal region originates from neural crest and placodal lineages.
• Understanding olfactory system development is crucial for addressing congenital disorders.

Purpose of the Study:

• To create a molecular and spatial atlas of the early human fetal nasal region.
• To identify cell types and gene expression dynamics during olfactory development.
• To investigate the "one neuron-one receptor" principle in early olfactory sensory neurons.

Main Methods:

• Integrated single-nucleus RNA sequencing (snRNA-seq) and multiplexed error-robust fluorescence in situ hybridization (MERFISH).
• Analysis of human fetal nasal tissue from 7 to 12 post-conceptional weeks.
• Spatial and temporal mapping of gene expression in the olfactory epithelium (OE) and surrounding tissues.

Main Results:

• Resolved 32 distinct cell types within the developing nasal region.
• Identified key markers for olfactory sensory neuron differentiation and OE patterning.
• Provided molecular evidence for the "one neuron-one receptor" principle in the first trimester.
• Mapped expression dynamics of 169 olfactory receptor genes.

Conclusions:

• Established a comprehensive molecular and spatial framework for early human olfactory development.
• Provides a valuable resource for research on sensory neurogenesis.
• Offers foundational data for studying congenital olfactory disorders.