2026-08-05 スタンフォード大学
Emma Vidal
＜関連情報＞
- https://news.stanford.edu/stories/2026/08/aging-brain-immune-system-research
- https://www.nature.com/articles/s41586-026-10939-0
体細胞変異は、ヒトの加齢におけるミクログリアの発生過程を明らかにする Somatic mutations reveal the ontogeny of microglia in human aging
Julia A. Belk,Yaowen Zhang,Emily E. Reilly,Quanming Shi,Daniel Dan Liu,Nicole Womack-Gambrel,Maarten van der Linde,Lisa Ma,Debasmita Paul,Alejandro Medina Enciso,Raja Kalluru,Jacob Weiss,Rui Li,Anna E. Eastman,Chunfang Zhu,Arnav Chakravarthy,Syed Bukhari,Dipabarna Bhattacharya,Suyash Raj,Daniel Richard,Simone Brioschi,Matthew R. Chrostek,Daniel C. Nachun,Christopher M. Arends,… Siddhartha Jaiswal
Nature Published: 30 July 2026 Unedited version
Abstract
Microglia are the resident macrophages of the central nervous system1. In mice, microglia seed the brain during embryogenesis and can be maintained throughout life with minimal input from adult hematopoiesis2-4. The origins of human microglia are less clear, but recent evidence suggests that marrow-derived cells contribute to the human microglial pool in certain individuals5-9. Here, to investigate the ontogeny of human microglia, we develop an approach that uses the collection of accumulated somatic mutations which uniquely labels each clone of cells to track the infiltration of marrow-derived cells into the human brain. Applying this approach to 20 aged individuals, we find evidence of an influx of marrow-derived cells into the brain in all examined individuals. Single cell analysis, including single cell lineage tracing using mitochondrial DNA variants, demonstrates that these infiltrating cells are similar to microglia and can comprise a large fraction of the microglial pool. Analysis of human cohort data demonstrates a protective association between most types of clonal hematopoiesis and Alzheimer’s disease. In sum, this work uncovers a widespread influx of myeloid cells into the healthy human brain which contributes to the pool of human microglia and becomes common with aging.
