美国斯坦福大学Karl Deisseroth等研究职员相助实现小脑颗粒细胞三维基因组结构的终生重构。该项研究效果揭晓在2023年9月8日出书的《科学》杂志上。
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)生长为群体规模(Pop-C)和病毒富集(vDip-C)模式,研究职员首次剖析了单个小脑细胞的三维基因组结构,为人类和小鼠建设了跨越生命周期的三维基因组图谱,并团结丈量了发育历程中的转录组和染色质可及性。研究职员发明,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历程中会逐渐重塑,建设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。
这些效果展现了意想不到的演化守旧分子历程,它们是哺乳动物整个生命周期中神经发育和朽迈的奇异特征的基础。
据悉,小脑包括了人脑中的大部分神经元,并体现出奇异的发育和朽迈模式。
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:《科学》,创刊于1880年。隶属于美国科学增进会,最新IF:63.714
官方网址:https://www.sciencemag.org/
投稿链接:https://cts.sciencemag.org/scc/