Sibling chimerism among microglia in marmosets.

Area of Science:

• Developmental Biology
• Immunology
• Neuroscience

Background:

• Chimerism is rare in mammals but common in marmosets due to fused circulatory systems during twin/triplet development.
• Previous observations of Y-chromosome DNA in female marmoset organs suggested widespread chimerism, but the cell types involved remained unclear.

Approach:

• Analyzed single-cell RNA sequencing data from marmoset blood, liver, kidney, and brain tissues.
• Utilized transcribed single nucleotide polymorphisms (SNPs) to identify sibling-derived cells across various tissue types.
• Quantified chimerism in hematopoietic cells, microglia, macrophages, and other brain-resident cells.

Key Points:

• Sibling-derived chimerism across all analyzed tissues originated exclusively from hematopoietic cells (myeloid and lymphoid lineages).
• In the brain, chimerism was observed in microglia and macrophages, but not in neurons, glia, or ependymal cells.
• Microglial chimerism varied significantly across brain regions, suggesting localized responses or clonal expansion.

Conclusions:

• Naturally occurring marmoset chimerism provides a unique model to study the influence of genes, mutations, and brain environment on microglial biology.
• This model allows for the differentiation of microglial contributions versus other cell types in shaping brain phenotypes.
• Microglial gene expression is more influenced by local context than by sibling genetic differences.