Dynamic Lamin B1-Gene Association During Oligodendrocyte Progenitor Differentiation.
Dynamic Lamin B1-Gene Association During Oligodendrocyte Progenitor Differentiation.
复制标题
少突胶质细胞祖细胞分化过程中的动态核纤层蛋白 B1 基因关联。
DOI：
10.1007/s11064-019-02941-y
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发表时间：
2020
影响因子：
4.4
通讯作者：
Casaccia,Patrizia
中科院分区：
文献类型：
--
作者：
Yattah,Camila;Hernandez,Marylens;Huang,Dennis;Park,HyeJin;Liao,Will;Casaccia,Patrizia
少突胶质细胞（OL）从祖细胞（OPC）的分化是一个独特的基因表达程序的结果，这是进一步调节的拓扑结构域的形成与核纤层。在这项研究中，我们表明，培养的OPC的特点是逐步下降的内源性核纤层蛋白B1（LMNB 1）的水平在分化成OL。然后，我们确定的基因动态相关的核纤层组件LMNB 1在此过渡期间，使用一个完善的技术称为DamID，这是基于细菌衍生的脱氧腺苷甲基化酶（大坝）的能力，修改基因组区域的密切联系。我们在OPC中表达了含有Dam和LMNB 1的融合蛋白（OPCLMNB 1-Dam），并使它们保持增殖或分化成OL（OLLMNB 1-Dam），并鉴定了与分化动态相关的LMNB 1基因。重要的是，我们确定了Lss，编码羊毛甾醇合成酶，胆固醇合成中的关键酶的基因，与OLLMNB 1-Dam的核纤层相关。这一发现至少可以部分解释先前报道的以少突胶质细胞中持续LMNB 1表达为特征的ADLD小鼠模型的脂质失调。
Differentiation of oligodendrocytes (OL) from progenitor cells (OPC) is the result of a unique program of gene expression, which is further regulated by the formation of topological domains of association with the nuclear lamina. In this study, we show that cultured OPC were characterized by progressively declining levels of endogenous Lamin B1 (LMNB1) during differentiation into OL. We then identify the genes dynamically associated to the nuclear lamina component LMNB1 during this transition, using a well established technique called DamID, which is based on the ability of a bacterially-derived deoxyadenosine methylase (Dam), to modify genomic regions in close proximity. We expressed a fusion protein containing Dam and LMNB1 in OPC (OPCLMNB1-Dam) and either kept them proliferating or differentiated them into OL (OLLMNB1-Dam) and identified genes that were dynamically associated to LMNB1 with differentiation. Importantly, we identifiedLss, the gene encoding for lanosterol synthase, a key enzyme in cholesterol synthesis, as associated to the nuclear lamina in OLLMNB1-Dam. This finding could at least in part explain the lipid dysregulation previously reported for mouse models of ADLD characterized by persistent LMNB1 expression in oligodendrocytes.