来自以色列希伯莱大学医学院的研究人员日前发现在早期造血干细胞中,单个细胞可以选择两种等位基因,但当它们发展时它们仅偏向其中一种等位基因。

-2012年10月25日《自然》


中文翻译


【题目】免疫球蛋白κ重排的克隆等位先决条件

【译文】尽管大多数基因的两个等位位点都会表达,但很多关键的基因组位点——包括免疫和嗅觉感受器区域——受到随机方式单等位基因地控制,以及一些在靶组织中表达母本等位基因和父本等位基因的细胞。关于发育阶段这种现象是如何被调控和编程的,我们知之甚少。本研究利用小鼠免疫球蛋白κ (Igκ)作为模型系统,证实了尽管单个造血干细胞特征为等位塑造性,但早期淋巴谱系细胞开始热衷于单个等位基因的选择,而且这种决定以一种克隆方式被稳定维持,这种克隆方式预先决定了B细胞中单等位基因重排。这在分子水平伴随着以不同步复制周期模式在κ座位上潜在的等位变化。这些实验可能有助于定义一种干细胞可塑性的新概念。

英文原稿


[Title]: Clonal allelic predetermination of immunoglobulin-κ rearrangement

 [Authors]:Marganit Farago,1, 7 Chaggai Rosenbluh,1, 7 Maya Tevlin,1, 8, 7 Shira Fraenkel,1 Sharon Schlesinger,1 Hagit Masika,1 Masha Gouzman,1 Grace Teng,2 David Schatz,2, 3 Yoach Rais,4 Jacob H. Hanna,4 Alexander Mildner,5 Steffen Jung,5 Gustavo Mostoslavsky,6 Howard Cedar1 & Yehudit Bergman1

[Abstract]Although most genes are expressed biallelically, a number of key genomic sites—including immune and olfactory receptor regions—are controlled monoallelically in a stochastic manner, with some cells expressing the maternal allele and others the paternal allele in the target tissue. Very little is known about how this phenomenon is regulated and programmed during development. Here, using mouse immunoglobulin-κ (Igκ) as a model system, we demonstrate that although individual haematopoietic stem cells are characterized by allelic plasticity, early lymphoid lineage cells become committed to the choice of a single allele, and this decision is then stably maintained in a clonal manner that predetermines monoallelic rearrangement in B cells. This is accompanied at the molecular level by underlying allelic changes in asynchronous replication timing patterns at the κ locus. These experiments may serve to define a new concept of stem cell plasticity.

原文地址

http://www.nature.com/nature/journal/v490/n7421/full/nature11496.html

 

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