美國斯坦福大學(xué)Karl Deisseroth等研究人員合作實(shí)現(xiàn)小腦顆粒細(xì)胞三維基因組結(jié)構(gòu)的終生重構(gòu)。該項(xiàng)研究成果發(fā)表在2023年9月8日出版的《科學(xué)》雜志上。
通過將單細(xì)胞三維（3D）基因組檢測：二倍體染色體構(gòu)象捕獲（或稱Dip-C）發(fā)展為群體規(guī)模（Pop-C）和病毒富集（vDip-C）模式，研究人員首次解析了單個(gè)小腦細(xì)胞的三維基因組結(jié)構(gòu)，為人類和小鼠創(chuàng)建了跨越生命周期的三維基因組圖譜，并聯(lián)合測量了發(fā)育過程中的轉(zhuǎn)錄組和染色質(zhì)可及性。研究人員發(fā)現(xiàn)，雖然小腦顆粒神經(jīng)元的轉(zhuǎn)錄組和染色質(zhì)可及性在出生后早期就已成熟，但三維基因組結(jié)構(gòu)在整個(gè)生命過程中會(huì)逐漸重塑，建立超長距離的染色體內(nèi)接觸和特定的染色體間接觸，這在神經(jīng)元中很少見。
這些結(jié)果揭示了意想不到的演化保守分子過程，它們是哺乳動(dòng)物整個(gè)生命周期中神經(jīng)發(fā)育和衰老的獨(dú)特特征的基礎(chǔ)。
據(jù)悉，小腦包含了人腦中的大部分神經(jīng)元，并表現(xiàn)出獨(dú)特的發(fā)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(xué)》，創(chuàng)刊于1880年。隸屬于美國科學(xué)促進(jìn)會(huì)，最新IF：63.714
官方網(wǎng)址：https://www.sciencemag.org/
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