Sibling chimerism among microglia in marmosets

Chimerism, a phenomenon more common in certain mammal species, was recently observed in marmosets at a rate of 12-80%. This unusual occurrence stems from the unique in utero connections among fraternal twins or triplets, which facilitate the circulation of stem cells. Notably, the presence of Y-chromosome DNA sequences in the organs of female marmosets has long hinted at the potential influence of chimerism on these organs.

However, it remained unclear whether this chimerism was primarily driven by blood-derived cells or also involved contributions from other cell types.

To clarify this matter, researchers examined single-cell RNA-seq data from blood, liver, kidney, and multiple brain regions in various marmosets. By utilizing transcribed single-nucleotide polymorphisms (SNPs), they identified cells with the same genetic makeup as their sibling within different cell types across these tissues. The findings revealed that sibling-derived chimerism in all tissues was entirely due to cells originating from the hematopoietic lineage, specifically myeloid and lymphoid lineages.

In brain tissue, this chimerism manifested as sibling-derived microglia (20-52%) and macrophages (18-64%), while other resident cell types such as neurons, glia, or ependymal cells remained unaffected. Importantly, the percentage of microglia that were of sibling origin varied significantly across different brain regions within individual animals, suggesting that local recruitment, proliferation cues, clonal expansion histories, or distinct clonal expansion histories in different brain areas could be responsible.

Upon closer examination, the gene expression profiles of microglia displayed a much stronger association with their local or host context rather than with sibling genetic differences. This discovery holds significant implications for understanding the effects of genes, mutations, and brain contexts on microglial biology. Furthermore, it offers a means to differentiate the roles of microglia from those of other cell types in shaping brain phenotypes in naturally occurring marmoset chimerism.