文章：

骨髓细胞中的生态位调节和生态位调节基因

Niche-modulated and niche-modulating genes in bone marrow cells

原文发布日期：2012-12-14

DOI: 10.1038/bcj.2012.42

类型: Original Article

开放获取: 是

英文摘要：

Bone marrow (BM) cells depend on their niche for growth and survival. However, the genes modulated by niche stimuli have not been discriminated yet. For this purpose, we investigated BM aspirations from patients with various hematological malignancies. Each aspirate was fractionated, and the various samples were fixed at different time points and analyzed by microarray. Identification of niche-modulated genes relied on sustained change in expression following loss of niche regulation. Compared with the reference (‘authentic’) samples, which were fixed immediately following aspiration, the BM samples fixed after longer stay out-of-niche acquired numerous changes in gene-expression profile (GEP). The overall genes modulated included a common subset of functionally diverse genes displaying prompt and sustained ‘switch’ in expression irrespective of the tumor type. Interestingly, the ‘switch’ in GEP was reversible and turned ‘off-and-on’ again in culture conditions, resuming cell–cell–matrix contact versus respread into suspension, respectively. Moreover, the resuming of contact prolonged the survival of tumor cells out-of-niche, and the regression of the ‘contactless switch’ was followed by induction of a new set of genes, this time mainly encoding extracellular proteins including angiogenic factors and extracellular matrix proteins. Our data set, being unique in authentic expression design, uncovered niche-modulated and niche-modulating genes capable of controlling homing, expansion and angiogenesis.

摘要翻译： 

骨髓（BM）细胞的生长与存活依赖于其微环境。然而，由微环境刺激调控的基因尚未被明确区分。为此，我们研究了来自不同血液系统恶性肿瘤患者的骨髓穿刺样本。每份穿刺液经分馏处理后，在不同时间点对各类样本进行固定并通过微阵列技术进行分析。微环境调控基因的鉴定依据脱离微环境调控后基因表达的持续性变化。与穿刺后立即固定的参照（“真实”）样本相比，脱离微环境较长时间后固定的骨髓样本获得了大量基因表达谱（GEP）的改变。被调控的基因整体中包含一个功能多样的共同亚集，这些基因不论肿瘤类型如何均表现出迅速而持续的表达“开关”现象。有趣的是，这种GEP的“开关”具有可逆性，在培养条件下通过恢复细胞-细胞-基质接触 versus 重新悬浮可分别实现“关闭与开启”的循环。此外，细胞接触的恢复能延长肿瘤细胞在脱离微环境后的存活时间，而“无接触开关”的消退会诱导新一轮基因表达，这次主要编码包括血管生成因子和细胞外基质蛋白在内的胞外蛋白。我们具有真实表达设计独特性的数据集，揭示了能够控制归巢、扩张和血管生成的微环境调控基因及微环境修饰基因。

原文链接：

Niche-modulated and niche-modulating genes in bone marrow cells