Spatial transcriptomic brain imaging reveals the effects of immunomodulation therapy on specific regional brain cells in a mouse dementia model

• Published in: BMC genomics Vol. 25; no. 1; p. 516
• Main Authors: Lee, Eun Ji, Suh, Minseok, Choi, Hongyoon, Choi, Yoori, Hwang, Do Won, Bae, Sungwoo, Lee, Dong Soo
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 25.05.2024; BioMed Central; BMC
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - therapy; Alzheimer's disease; Analysis; Animals; Antibodies; Bar codes; Behavior; Biodistribution; Brain; Brain - diagnostic imaging; Brain - metabolism; Brain - pathology; Brain architecture; Brain imaging; Care and treatment; CD4 antigen; Cell state annotation; Cell type decomposition; Cells; Dementia - genetics; Dementia - therapy; Dementia disorders; Diagnosis; Disease Models, Animal; DNA barcoding; Drug development; Drug dosages; Encephalomyelitis; Gene Expression Profiling; Genes; Immunoglobulins; Immunomodulation; Immunomodulation - drug effects; Immunomodulators; Immunotherapy; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Lymphocytes; Major brain cells; Medical imaging; Mice; Natural killer cells; Neurodegenerative diseases; Neuroimaging; Patient outcomes; Rare immune cells; Signatures; Spatial transcriptomics; Transcriptome; Transcriptomics; Workflow; South Korea; Rare immune cells; Brain imaging; Major brain cells; Spatial transcriptomics; Cell type decomposition; Immunomodulatory therapy; Cell state annotation
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-024-10434-8

Increasing evidence of brain-immune crosstalk raises expectations for the efficacy of novel immunotherapies in Alzheimer's disease (AD), but the lack of methods to examine brain tissues makes it difficult to evaluate therapeutics. Here, we investigated the changes in spatial transcriptomic signatures and brain cell types using the 10x Genomics Visium platform in immune-modulated AD models after various treatments. To proceed with an analysis suitable for barcode-based spatial transcriptomics, we first organized a workflow for segmentation of neuroanatomical regions, establishment of appropriate gene combinations, and comprehensive review of altered brain cell signatures. Ultimately, we investigated spatial transcriptomic changes following administration of immunomodulators, NK cell supplements and an anti-CD4 antibody, which ameliorated behavior impairment, and designated brain cells and regions showing probable associations with behavior changes. We provided the customized analytic pipeline into an application named STquantool. Thus, we anticipate that our approach can help researchers interpret the real action of drug candidates by simultaneously investigating the dynamics of all transcripts for the development of novel AD therapeutics.