Medical Institute of Bioregulation, Kyushu University

Title

Tracking reactive microglial state across the lifespan

Speaker

Qingyun Li, PhD
Assistant Professor
Department of Neuroscience, Washington University in St. Louis School of Medicine

Date

Aug 3 (Mon), 2026
16：00〜17：00

Venue

Lecture Room 102, 1F, Biomedical Research Station, Hospital Campus
(Building No. 35 on the [Campus Map])

Abstract

Single-cell RNA sequencing studies have revealed transcriptionally distinct microglial states across development, aging, and disease. These include proliferative region–associated microglia (PAMs) in the developing white matter, disease-associated microglia (DAMs) common to many neurodegenerative conditions, and white matter–associated microglia (WAMs) in the aged brain, among others. Interestingly, PAMs, DAMs, and WAMs share a core gene signature and overlapping functional properties. However, it remains unclear whether these subsets represent ontogenically distinct lineages or instead reflect plastic transitions of microglial states driven by converging signals. The temporal dynamics, regulatory mechanisms, and functional implications of microglial state changes also remain poorly understood. Using a specific inducible driver line, Clec7a-CreERT2, recently developed by us, we track PAMs and DAMs across conditions and lifespan, revealing the extraordinary plasticity of reactive microglial states. We further employ highly sensitive epigenomic profiling to identify the cis- and trans-regulatory elements that govern these transitions. These studies uncover the intricate relationships and dynamic nature of spatially and temporally discrete microglial states in health and disease.

References

1. Li Q*, Cheng Z, Zhou L, Darmanis S, Neff NF, Okamoto J, Gulati G, Bennett ML, Sun LO, Clarke LE, Marschallinger J, Yu G, Quake SR, Wyss-Coray T, Barres BA. Developmental heterogeneity of microglia and brain myeloid cells revealed by deep single-cell RNA sequencing. Neuron. 2019 Jan 16;101(2):207-223.e10.
2. Barclay KM, Abduljawad N, Cheng Z, Kim MW, Zhou L, Yang J, Rustenhoven J, Mazzitelli Perez J, Smyth LCD, Kapadia D, Brioschi S, Beatty W, Hou JC, Saligrama N, Colonna M, Yu G, Kipnis J, Li Q*. An inducible genetic tool for tracking and manipulating specific microglial states in development and disease. Immunity. 2024 Jun 11;57(6):1394-1412.e8.
3. Hamagami N, Kapadia D, Barclay KM, Huang Y, Abduljawad N, Cheng Z, McLaughlin L, Singhania D, Ding X, Yang J, Sun Z, Karra V, Du S, Bayguinov P, Yu G, Li YE, Gabel HW*, Li Q*. State-specific enhancer landscapes govern microglial plasticity. Immunity. 2026 Feb 10;59(2):288-305.e11.
4. Naz H, Palovics R, Yamada S, Lu N, Wyss-Coray T, Li Q*, Zhao G*. Core activation program and selective responsiveness of microglia in aging and parabiosis. bioRxiv. 2025. In revision. doi: https://doi.org/10.1101/2025.10.29.685417.

Contact

Takahiro Masuda
Division of Molecular Neuroimmunology, Medical Institute of Bioregulation
TEL: 092 (642) 6800
E-mail: takahiro.masuda[＠]bioreg.kyushu-u.ac.jp
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