Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Schwarzer A

PROVIDER: S-EPMC5550424 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Schwarzer Adrian A Emmrich Stephan S Schmidt Franziska F Beck Dominik D Ng Michelle M Reimer Christina C Adams Felix Ferdinand FF Grasedieck Sarah S Witte Damian D Käbler Sebastian S Wong Jason W H JWH Shah Anushi A Huang Yizhou Y Jammal Razan R Maroz Aliaksandra A Jongen-Lavrencic Mojca M Schambach Axel A Kuchenbauer Florian F Pimanda John E JE Reinhardt Dirk D Heckl Dirk D Klusmann Jan-Henning JH

Nature communications 20170809 1

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 i ...[more]

PMID: 28794406

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Project description:Simple Summary Survival rates for children with acute myeloid leukemia have significantly improved in recent decades. Still, 20–30% will succumb to therapy-related toxicity and relapse. Research has shown that leukemic stem cells (LSCs) in particular are responsible for relapse. Therefore, the characterization of the LSC is needed to improve the current treatment options for and survival of these pediatric patients. Previously, research has focused mainly on the protein-coding part of the human genome, but recently the focus has also shifted to non-coding genes, including long non-coding RNA (lncRNA) and microRNA (miRNA). The aim of this study was to investigate the expression of lncRNAs and miRNAs in pediatric AML subpopulations (LSCs and leukemic blasts) and their normal counterparts (hematopoietic stem cells and control myeloblasts). We provide here a unique set of non-coding RNAs with a potential role in the pathogenesis of pediatric AML, paving the way for further translational research studies. Abstract Pediatric acute myeloid leukemia (pedAML) is a heterogeneous blood cancer that affects children. Although survival rates have significantly improved over the past few decades, 20–30% of children will succumb due to treatment-related toxicity or relapse. The molecular characterization of the leukemic stem cell, shown to be responsible for relapse, is needed to improve treatment options and survival. Recently, it has become clear that non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play a role in the development of human diseases, including pediatric cancer. Nevertheless, non-coding RNA expression data in pedAML are scarce. Here, we explored lncRNA (n = 30,168) and miRNA (n = 627) expression in pedAML subpopulations (leukemic stem cells (LSCs) and leukemic blasts (L-blasts)) and their normal counterparts (hematopoietic stem cells and control myeloblasts). The potential regulatory activity of differentially expressed lncRNAs in LSCs (unique or shared with the L-blast comparison) on miRNAs was assessed. Moreover, pre-ranked gene set enrichment analyses of (anti-) correlated protein-coding genes were performed to predict the functional relevance of the differentially upregulated lncRNAs in LSCs (unique or shared with the L-blast comparison). In conclusion, this study provides a catalog of non-coding RNAs with a potential role in the pathogenesis of pedAML, paving the way for further translational research studies.

Dataset Information

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

Publications

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

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