通过将单细胞三维（3D）基因组检测：二倍体染色体构象捕获（或称Dip-C）发展为群体规模（Pop-C）和病毒富集（vDip-C）模式，研究人员首次解析了单个小脑细胞的三维基因组结构，为人类和小鼠创建了跨越生命周期的三维基因组图谱，并联合测量了发育过程中的转录组和染色质可及性。研究人员发现，虽然小脑颗粒神经元的转录组和染色质可及性在出生后早期就已成熟，但三维基因组结构在整个生命过程中会逐渐重塑，建立超长距离的染色体内接触和特定的染色体间接触，这在神经元中很少见。
这些结果揭示了意想不到的演化保守分子过程，它们是哺乳动物整个生命周期中神经发育和衰老的独特特征的基础。
据悉，小脑包含了人脑中的大部分神经元，并表现出独特的发育和衰老模式。
附：英文原文
Title: Lifelong restructuring of 3D genome architecture in cerebellar granule cells
Author: Longzhi Tan, Jenny Shi, Siavash Moghadami, Bibudha Parasar, Cydney P. Wright, Yunji Seo, Kristen Vallejo, Inma Cobos, Laramie Duncan, Ritchie Chen, Karl Deisseroth
Issue&Volume: 2023-09-08
Abstract: 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.
DOI: adh3253
Source: https://www.science.org/doi/full/10.1126/science.adh3253