Bone marrow cells replenish microglia in the aging human brain
Bone marrow cells replenish microglia in the aging human brain
On 30 July, researchers reported in a Nature paper that they had traced the origins of immune cells in the brains of 20 older donors. Every sample contained descendants of bone marrow cells that resembled microglia, the brain's resident immune cells.
Microglia clear cellular debris and respond to injury. In mouse experiments, they colonize the brain before birth and then proliferate locally. Julia Belk's group investigated whether the aging human brain follows the same pattern.
Dividing cells gradually acquire random DNA mutations, which their descendants inherit. The researchers used these somatic mutations as lineage markers and compared them in blood, bone marrow, and brain cells. Matching mutations showed that several myeloid lineages had migrated from the bone marrow into the brain.
Single-cell analysis and mitochondrial DNA variants showed that these cells resembled microglia. In some samples, they accounted for a large proportion of the microglial pool. Among the oldest donors, larger blood clones were associated with more descendants of those clones in the brain.
The authors propose the following model: with age, blood-derived cells replace some microglia of embryonic origin. Under this model, the state of the bone marrow alters the brain's immune environment by changing the composition of the cells that enter it.
Studies have reported different associations with Alzheimer's disease. In the human cohorts examined by the Nature authors, most types of clonal hematopoiesis were associated with a lower incidence of the disease. In a Cell paper published in June, another group examined 311 brain samples from people with Alzheimer's disease and found microglia-like cells carrying mutations from expanded hematopoietic clones and showing signs of inflammation. Researchers can now look for the same cell lineage in blood and brain instead of measuring only the overall level of inflammation.