Integrated analysis of the human hematopoietic non-coding RNA landscape reveals lncRNA-stem cell signature in AML

Long non-coding RNAs (lncRNAs) and miRNAs have emerged as crucial regulators of gene expression and cell fate decisions. We defined the ncRNA landscape of the human blood system to map each blood cell population by its unique lncRNA expression portrait. Exploiting co-expression of functionally related genes, we allocated cell type-specific fingerprint lncRNAs to critical regulatory circuits of the hematopoietic system. The granulocyte fingerprint gene LINC00173 was predicted to control differentiation and proliferation of myeloid cells in association with PRC2, and with this lncRNA we verified the strength of our pipeline. Following incorporation of pediatric acute myeloid leukemia (AML) samples into the landscape, we revealed an lncRNA stem cell signature shared between AML samples and healthy HSCs that predicted survival in an independent cohort of 177 AML samples. Thus, we provide a comprehensive resource for exploration of the non-coding landscape across the entire human blood hierarchy.