Sibling chimerism among microglia in marmosets

Area of Science:

• Comparative genomics
• Developmental biology
• Neuroscience

Background:

• Chimerism is rare in mammals but common in marmosets due to shared placental circulation in fraternal twins.
• Previous observations of Y-chromosome DNA in female marmoset organs suggested organ chimerism, but the cell types involved were unknown.

Purpose of the Study:

• To determine if marmoset organ chimerism involves blood-derived cells or other cell types.
• To investigate the cellular basis of chimerism in marmoset tissues, including the brain.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) was used to analyze tissues from marmosets.
• Transcribed single-nucleotide polymorphisms (SNPs) identified sibling-derived cells within various tissue types.

Main Results:

• Sibling-derived chimerism in 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, with gene expression more influenced by local context than genetic origin.

Conclusions:

• Marmoset chimerism is driven by hematopoietic stem cells, affecting specific immune cell populations in tissues.
• This study clarifies the cellular contribution to chimerism, essential for understanding microglial biology and brain phenotypes.
• Naturally occurring chimerism in marmosets offers a unique model for studying gene, mutation, and brain context effects on microglia.