Debasmita Paul

All Publications

• Somatic mutations reveal the ontogeny of microglia in human ageing. Nature Belk, J. A., Zhang, Y., Reilly, E. E., Shi, Q., Liu, D. D., Womack-Gambrel, N., van der Linde, M., Ma, L., Paul, D., Enciso, A. M., Kalluru, R., Weiss, J., Li, R., Eastman, A. E., Zhu, C., Chakravarthy, A., Bukhari, S., Bhattacharya, D., Raj, S., Richard, D., Brioschi, S., Chrostek, M. R., Nachun, D. C., Arends, C. M., Gopakumar, J., Tengesdal, I. W., Bynum, A., Mitchell, S., Sandor, K., Zhang, W., Vardarajan, B. N., Cobos, I., Born, D. E., West, R. B., Brunet, A., Colonna, M., Bharani, K. L., Vogel, H., Montine, T. J., Latimer, C. S., Weissman, I. L., Matusiak, M., Hooper, J. E., Keene, C. D., Chang, H. Y., Jaiswal, S. 2026

  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 haematopoiesis2-4. The origins of human microglia are less clear, but recent evidence suggests that bone-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 that uniquely labels each clone of cells to track the infiltration of bone-marrow-derived cells into the human brain. Applying this approach to 20 older individuals, we find evidence of an influx of bone-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 haematopoiesis and Alzheimer's disease. Together, we identify a widespread influx of myeloid cells into the healthy human brain that contributes to the pool of human microglia and becomes common with ageing.

  View details for DOI 10.1038/s41586-026-10939-0

  View details for PubMedID 42686898

  View details for PubMedCentralID 3719181

• Development of methods for enriching microglia nuclei from frozen brain samples to study the effect of CHIP on Alzheimer's disease Bhattacharya, D., Weiss, J., Enciso, A., Paul, D., Bynum, A., Zhang, Y., Nachun, D., Jaiswal, S. ELSEVIER. 2025: 4947-4948

  View details for DOI 10.1182/blood-2025-4947

  View details for Web of Science ID 001661718200047