美國斯坦福大學Karl Deisseroth等研究人員合作實現小腦顆粒細胞三維基因組結構的終生重構。該項研究成果發表在2023年9月8日出版的《科學》雜志上。
通過將單細胞三維（3D）基因組檢測：二倍體染色體構象捕獲（或稱Dip-C）發展為群體規模（Pop-C）和病毒富集（vDip-C）模式，研究人員首次解析了單個小腦細胞的三維基因組結構，為人類和小鼠創建了跨越生命周期的三維基因組圖譜，并聯合測量了發育過程中的轉錄組和染色質可及性。研究人員發現，雖然小腦顆粒神經元的轉錄組和染色質可及性在出生后早期就已成熟，但三維基因組結構在整個生命過程中會逐漸重塑，建立超長距離的染色體內接觸和特定的染色體間接觸，這在神經元中很少見。
這些結果揭示了意想不到的演化保守分子過程，它們是哺乳動物整個生命周期中神經發育和衰老的獨特特征的基礎。
據悉，小腦包含了人腦中的大部分神經元，并表現出獨特的發育和衰老模式。
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
期刊信息
Science：《科學》，創刊于1880年。隸屬于美國科學促進會，最新IF：63.714
官方網址：https://www.sciencemag.org/
投稿鏈接：https://cts.sciencemag.org/scc/
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