Clonal hematopoiesis-associated motoric deficits caused by monocyte-derived microglia accumulating in aging mice
Kim JS, Trzebanski S, Shin SH, Schori L, Frumer Friedman GR, Ilani NC, Kadam A, Vicario R, Aust O, Bugaeva P, Piatek S, Ismajli LK, Hoffmann CJ, Scheller M, Boura-Halfon S, Kaushansky N, Golani O, Solomon A, Liu Z, Amann L, Böhm-Sturm P, Koch SP, Wenger N, Ginhoux F, Prinz M, Avraham R, Harms C, Geissmann F, Müller-Tidow C, Uderhardt S, Milenkovic I, Shlush L, Jung S (2025)
Publication Type: Journal article
Publication year: 2025
Journal
Book Volume: 44
Article Number: 115609
Journal Issue: 5
DOI: 10.1016/j.celrep.2025.115609
Abstract
Microglia are parenchymal brain macrophages that are established during embryogenesis and form a self-containing cellular compartment that resists seeding with cells derived from adult definitive hematopoiesis. We report that monocyte-derived macrophages (MoMΦs) accumulate in the brain of aging mice with distinct topologies, including the nigrostriatum and medulla but not the frontal cortex. Parenchymal MoMΦs adopt bona fide microglia morphology and expression profiles. Due to their hematopoietic stem cell (HSC) derivation, monocyte-derived microglia (MoMg) are unlike yolk-sac-derived cells, targets of clonal hematopoiesis (CH). Indeed, using a chimeric transfer model, we show that the hematopoietic expression of DNMT3AR882H, a prominent human CH variant, renders MoMg pathogenic and promotes motor deficits resembling atypical Parkinsonian disorders. Collectively, we establish that MoMg progressively seed the brain of healthy aging mice, accumulate in selected areas, and, when carrying a somatic mutation associated with CH, can cause brain pathology.
Authors with CRIS profile
Involved external institutions
Weizmann Institute of Science
Israel (IL)
Universitätsklinikum Freiburg
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
Shanghai Jiao Tong University / 上海交通大学
China (CN)
Memorial Sloan Kettering Cancer Center
United States (USA) (US)
Universitätsklinikum Heidelberg
Germany (DE)
Medizinische Universität Wien
Austria (AT)
Israel (IL)
Universitätsklinikum Freiburg
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
Shanghai Jiao Tong University / 上海交通大学
China (CN)
Memorial Sloan Kettering Cancer Center
United States (USA) (US)
Universitätsklinikum Heidelberg
Germany (DE)
Medizinische Universität Wien
Austria (AT)
How to cite
APA:
Kim, J.S., Trzebanski, S., Shin, S.H., Schori, L., Frumer Friedman, G.R., Ilani, N.C.,... Jung, S. (2025). Clonal hematopoiesis-associated motoric deficits caused by monocyte-derived microglia accumulating in aging mice. Cell Reports, 44(5). https://doi.org/10.1016/j.celrep.2025.115609
MLA:
Kim, Jung Seok, et al. "Clonal hematopoiesis-associated motoric deficits caused by monocyte-derived microglia accumulating in aging mice." Cell Reports 44.5 (2025).
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