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Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters

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Published on: September 27, 2012

Spatial transcriptomic clocks reveal cell proximity effects in brain ageing.

Eric D Sun^1,2,3, Olivia Y Zhou^3,4,5, Max Hauptschein³

¹Biomedical Data Science Graduate Program, Stanford University, Stanford, CA, USA.

|December 18, 2024

Summary

This summary is machine-generated.

Brain aging involves cellular changes and unknown cell interactions. New spatial transcriptomics reveal T cells promote aging, while neural stem cells rejuvenate, offering targets for interventions.

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Area of Science:

Neuroscience
Genomics
Computational Biology

Background:

Cognitive decline and neurodegenerative disease risk increase with age.
Brain aging involves complex cellular changes, with the impact of aged cells on neighbors poorly understood.
Tools for studying cellular interactions in aging tissues are needed.

Purpose of the Study:

To create a spatially resolved single-cell transcriptomics brain atlas across the adult lifespan.
To develop spatial aging clocks to identify age-related transcriptomic changes and cell-cell interactions.
To investigate the effects of aging and rejuvenating interventions (exercise, partial reprogramming) on brain cells.

Main Methods:

Generated a large-scale spatial transcriptomics atlas of 4.2 million brain cells from 20 ages.
Developed machine learning-based spatial aging clocks to analyze transcriptomic fingerprints.
Utilized deep learning to assess cell-cell proximity effects.

Main Results:

Identified spatial and cell-type-specific signatures of aging, rejuvenation, and disease, including rare cell types.
Discovered that infiltrating T cells exert a pro-aging proximity effect, while neural stem cells have a pro-rejuvenating effect.
Identified potential mediators for these proximity effects.

Conclusions:

Rare cell types, like T cells and neural stem cells, significantly influence neighboring cells in the aging brain.
Targeting these cell types could offer strategies to counteract tissue aging.
Spatial aging clocks provide a scalable tool for studying cell-cell interactions and evaluating interventions.