lncRNA requirements for mouse acute myeloid leukemia and normal differentiation

Delas, M. J., Sabin, L. R., Dolzhenko, E., Knott, S. R., Munera Maravilla, E., Jackson, B. T., Wild, S. A., Kovacevic, T., Stork, E. M., Zhou, M., Erard, N., Lee, E., Kelley, D. R., Roth, M., Barbosa, I. S. A., Zuber, J., Rinn, J. L., Smith, A. D., Hannon, G. J. (2017) lncRNA requirements for mouse acute myeloid leukemia and normal differentiation. Elife, 6. e25607. ISSN 2050-084x

URL: https://www.ncbi.nlm.nih.gov/pubmed/28875933
DOI: 10.7554/eLife.25607

Abstract

A substantial fraction of the genome is transcribed in a cell type-specific manner, producing long non-coding RNAs (lncRNAs), rather than protein-coding transcripts. Here we systematically characterize transcriptional dynamics during hematopoiesis and in hematological malignancies. Our analysis of annotated and de novo assembled lncRNAs showed many are regulated during differentiation and mis-regulated in disease. We assessed lncRNA function via an in vivo RNAi screen in a model of acute myeloid leukemia. This identified several lncRNAs essential for leukemia maintenance, and found that a number act by promoting leukemia stem cell signatures. Leukemia blasts show a myeloid differentiation phenotype when these lncRNAs were depleted, and our data indicates that this effect is mediated via effects on the c-MYC oncogene. Bone marrow reconstitutions showed that a lncRNA expressed across all progenitors was required for the myeloid lineage, whereas the other leukemia-induced lncRNAs were dispensable in the normal setting.

Item Type: Paper
Uncontrolled Keywords: chromosomes developmental biology genes mouse stem cells
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosome
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function > chromosome

diseases & disorders > cancer > cancer types > leukemia
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > long non-coding RNA
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
CSHL Authors:
Communities: CSHL labs > Hannon lab
Depositing User: Matt Covey
Date Deposited: 08 Sep 2017 19:45
Last Modified: 08 Sep 2017 19:45
Related URLs:
URI: http://repository.cshl.edu/id/eprint/35279

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