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Single-Cell 3D Genome and Transcriptome Mapped Together in Alzheimer's Disease

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A team led by Jian Ma has published a study in Science applying their in-house GAGE-seq technology to read gene expression and three-dimensional chromatin structure simultaneously within the same nucleus. The work examined postmortem prefrontal cortex tissue from 20 ROSMAP donors: 10 with Alzheimer's disease and 10 age- and sex-matched non-AD donors. In Alzheimer's cells, the researchers found a higher proportion of long-range genomic interactions and increased mingling of A/B compartments, alongside reduced overall transcriptional output. Short-range regulatory-element interactions were weakened, while medium-range interactions anchored by CTCF were enhanced. The study links transcriptional decline in Alzheimer's disease to specific changes in 3D genome organization at single-cell resolution. How these structural alterations relate to disease progression, and whether they appear in other brain regions or earlier disease stages, remains open.

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Oct 28
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    Jian Ma Team Maps Single-Cell 3D Genome and Transcriptome Together in Alzheimer's Disease in Science

    Jian Ma's team published a study in Science using their in-house GAGE-seq technology to read gene expression and three-dimensional chromatin structure simultaneously in the same nucleus. They mapped postmortem prefrontal cortex from 20 ROSMAP donors: 10 with AD and 10 age- and sex-matched non-AD donors. AD cells showed a higher proportion of long-range interactions and increased A/B compartment mingling, with overall transcriptional output reduced, short-range regulatory-element interactions weakened, and medium-range CTCF-anchored interactions enhanced.

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