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Publication : Lifelong restructuring of 3D genome architecture in cerebellar granule cells.

First Author  Tan L Year  2023
Journal  Science Volume  381
Issue  6662 Pages  1112-1119
PubMed ID  37676945 Mgi Jnum  J:341207
Mgi Id  MGI:7532756 Doi  10.1126/science.adh3253
Citation  Tan L, et al. (2023) Lifelong restructuring of 3D genome architecture in cerebellar granule cells. Science 381(6662):1112-1119
abstractText  The cerebellum contains most of the neurons in the human brain and exhibits distinctive modes of development and aging. In this work, by developing our single-cell three-dimensional (3D) genome assay-diploid chromosome conformation capture, or Dip-C-into population-scale (Pop-C) and virus-enriched (vDip-C) modes, we resolved the first 3D genome structures of single cerebellar cells, created life-spanning 3D genome atlases for both humans and mice, and jointly measured transcriptome and chromatin accessibility during development. We found that although the transcriptome and chromatin accessibility of cerebellar granule neurons mature in early postnatal life, 3D genome architecture gradually remodels throughout life, establishing ultra-long-range intrachromosomal contacts and specific interchromosomal contacts that are rarely seen in neurons. These results reveal unexpected evolutionarily conserved molecular processes that underlie distinctive features of neural development and aging across the mammalian life span.
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