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Optics-free spatial genomics for mapping mammalian brain aging by IRISeq.
Abdulraouf Abdulraouf1,2,3, Weirong Jiang1, Zehao Zhang1,3
1Laboratory of Single Cell Genomics and Population Dynamics, The Rockefeller University, New York, NY, USA.
Nature Neuroscience
|May 12, 2026
Summary
New Imaging Reconstruction using Indexed Sequencing (IRISeq) technology maps mouse brain aging. Lymphocytes influence inflammation and senescence, revealing potential therapeutic targets for brain homeostasis.
Area of Science:
- Neuroscience
- Genomics
- Systems Biology
Background:
- Spatial transcriptomics enables in situ mapping of cellular heterogeneity and interactions.
- Existing methods face limitations in throughput, cost, and tissue coverage.
Purpose of the Study:
- Introduce Imaging Reconstruction using Indexed Sequencing (IRISeq) as a cost-effective platform for spatial transcriptomic profiling.
- Investigate region-specific aging signatures in mouse brains and the role of lymphocytes in brain aging.
Main Methods:
- Developed and applied the optics-free IRISeq platform for spatial transcriptomic profiling.
- Generated over 460,000 spatial transcriptome profiles from adult and aged mouse brains (wild-type, Rag1, Prkdc mutants).
- Integrated spatial data with 783,264 single-cell transcriptomes for comprehensive analysis.
Main Results:
- Identified region-specific aging signatures dependent on lymphocytes.
- Observed downregulation of interferon signaling and inflammation in ventricular regions upon lymphocyte depletion.
- Noted mutant-specific upregulation of senescence pathways and preserved ependymal cell abundance in lymphocyte-deficient models.
Conclusions:
- IRISeq offers a high-throughput, cost-effective solution for spatial transcriptomic profiling.
- Lymphocytes play a crucial role in driving inflammatory processes during brain aging.
- Findings highlight potential therapeutic targets for preserving brain homeostasis.
