The non-coding RNA landscape of human hematopoiesis and leukemia.

The non-coding RNA landscape of human hematopoiesis and leukemia.
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人类造血作用与白血病中的非编码RNA全景。

DOI:
10.1038/s41467-017-00212-4
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发表时间:
2017-08-09
影响因子:
16.6
通讯作者:
Klusmann JH
Klusmann JH
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Schwarzer A;Emmrich S;Schmidt F;Beck D;Ng M;Reimer C;Adams FF;Grasedieck S;Witte D;Käbler S;Wong JWH;Shah A;Huang Y;Jammal R;Maroz A;Jongen-Lavrencic M;Schambach A;Kuchenbauer F;Pimanda JE;Reinhardt D;Heckl D;Klusmann JH

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非编码RNA已成为基因表达和细胞命运决定的重要调节因子。然而,它们在正常和恶性人类造血过程中的表达模式和调节功能还不完全清楚。在这里,我们提出了一个全面的资源定义的非编码RNA景观的人类造血系统。基于每个血细胞群体的高度特异性非编码RNA表达画像,我们确定了独特的指纹非编码RNA-如粒细胞中的LINC 00173-并将其分配给参与血液稳态的关键调节回路。在将急性髓性白血病样本纳入景观后,我们进一步揭示了急性髓性白血病原始细胞和健康造血干细胞之间共享的与病理学相关的非编码RNA干细胞特征。我们的研究结果强调了非编码转录组在人类血液层次结构形成和维持中的重要性。虽然微RNA是造血和白血病发生的已知调节因子,但长非编码RNA的作用尚不清楚。在这里,作者提供了人类造血系统的非编码RNA表达景观,突出了它们在人类血液层次结构形成和维持中的作用。
Non-coding RNAs have emerged as crucial regulators of gene expression and cell fate decisions. However, their expression patterns and regulatory functions during normal and malignant human hematopoiesis are incompletely understood. Here we present a comprehensive resource defining the non-coding RNA landscape of the human hematopoietic system. Based on highly specific non-coding RNA expression portraits per blood cell population, we identify unique fingerprint non-coding RNAs—such as LINC00173 in granulocytes—and assign these to critical regulatory circuits involved in blood homeostasis. Following the incorporation of acute myeloid leukemia samples into the landscape, we further uncover prognostically relevant non-coding RNA stem cell signatures shared between acute myeloid leukemia blasts and healthy hematopoietic stem cells. Our findings highlight the importance of the non-coding transcriptome in the formation and maintenance of the human blood hierarchy. While micro-RNAs are known regulators of haematopoiesis and leukemogenesis, the role of long non-coding RNAs is less clear. Here the authors provide a non-coding RNA expression landscape of the human hematopoietic system, highlighting their role in the formation and maintenance of the human blood hierarchy.
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