이동수 (서울대학교 의과대학, 서울대학교병원) | 한빛사논문 > 한빛사

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조회418

서울대학교 의과대학, 서울대학교병원

Exp. Mol. Med., Dec 01 2023, | https://doi.org/10.1038/s12276-023-01123-9 Spatiotemporal characterization of glial cell activation in an Alzheimer's disease model by spatially resolved transcriptomics

Hongyoon Choi ^1,2,4,*, Eun Ji Lee ^1,3,4, Jin Seop Shin ^1,3, Hyun Kim ^1,3, Sungwoo Bae ^2,3, Yoori Choi ^1,2,3,* and Dong Soo Lee ^1,2,3,*

¹Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
²Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
³Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
⁴These authors contributed equally: Hongyoon Choi, Eun Ji Lee.

^*Corresponding authors: correspondence to Hongyoon Choi, Yoori Choi or Dong Soo Lee

Abstract

The molecular changes that occur with the progression of Alzheimer's disease (AD) are well known, but an understanding of the spatiotemporal heterogeneity of changes in the brain is lacking. Here, we investigated the spatially resolved transcriptome in a 5XFAD AD model at different ages to understand regional changes at the molecular level. Spatially resolved transcriptomic data were obtained from 5XFAD AD models and age-matched control mice. Differentially expressed genes were identified using spots clustered by anatomical structures. Gene signatures of activation of microglia and astrocytes were calculated and mapped on the spatially resolved transcriptomic data. We identified early alterations in the white matter (WM) of the AD model before the definite accumulation of amyloid plaques in the gray matter (GM). Changes in the early stage of the disease involved primarily glial cell activation in the WM, whereas the changes in the later stage of pathology were prominent in the GM. We confirmed that disease-associated microglia (DAM) and astrocyte (DAA) signatures also showed initial changes in WM and that activation spreads to GM. Trajectory inference using microglial gene sets revealed the subdivision of DAMs with different spatial patterns. Taken together, these results help to understand the spatiotemporal changes associated with reactive glial cells as a major pathophysiological characteristic of AD. The heterogeneous spatial molecular changes apply to identifying diagnostic and therapeutic targets caused by amyloid accumulation in AD.

논문정보

형식Research article
게재일2023년 12월 (BRIC 등록일 2023-12-04)
연구진국내 연구진
분야 바이오·의료융합 > 뇌인지과학

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