lncRNA Spehd Regulates Hematopoietic Stem and Progenitor Cells and Is Required for Multilineage Differentiation.
Jackson, Benjamin T
Munera Maravilla, Ester
Wild, Sophia A
Stork, Eva Maria
Knott, Simon RV
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Delás, M. J., Jackson, B. T., Kovacevic, T., Vangelisti, S., Munera Maravilla, E., Wild, S. A., Stork, E. M., et al. (2019). lncRNA Spehd Regulates Hematopoietic Stem and Progenitor Cells and Is Required for Multilineage Differentiation.. Cell reports, 27 (3), 719-729.e6. https://doi.org/10.1016/j.celrep.2019.03.080
Long non-coding RNAs (lncRNAs) show patterns of tissue- and cell-type-specific expression that are very similar to those of protein coding genes and consequently have the potential to control stem and progenitor cell fate decisions along a differentiation trajectory. To understand the roles that lncRNAs might play in hematopoiesis, we selected a subset of mouse lncRNAs with potentially relevant expression patterns and refined our candidate list using evidence of conserved expression in human blood lineages. For each candidate, we assessed its possible role in hematopoietic differentiation in vivo using competitive transplantation. Our studies identified two lncRNAs that were required for hematopoiesis. One of these, Spehd, showed defective multi-lineage differentiation, and its silencing yielded common myeloid progenitors deficient in their oxidative phosphorylation pathway. This effort not only suggests that lncRNAs can contribute to differentiation decisions during hematopoiesis but also provides a path toward the identification of functional lncRNAs in other differentiation hierarchies.
Hematopoietic Stem Cells, Cell Line, Tumor, Animals, Mice, Inbred C57BL, Mice, Trans-Activators, Proto-Oncogene Proteins, RNA, Small Interfering, Bone Marrow Transplantation, Regeneration, Cell Differentiation, Hematopoiesis, RNA Interference, Oxidative Phosphorylation, Cell Lineage, Female, GATA2 Transcription Factor, Cyclin-Dependent Kinase 6, RNA, Long Noncoding
This work was supported by Cancer Research UK. We specifically thank the Cancer Research UK Cambridge Institute Biological Resource Unit, Flow Cytometry, Research Instrumentation, Light Microscopy and Genomics Cores for their support throughout this project. M.J.D was supported by a PhD Fellowship from the Boehringer Ingelheim Fonds. G.J.H. is a Wellcome Trust Investigator, Royal Society Wolfson Research Professor, and was a Howard Hughes Medical Institute Investigator.
Cancer Research UK (C14303_do not transfer)
WELLCOME TRUST (110161/Z/15/Z)
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External DOI: https://doi.org/10.1016/j.celrep.2019.03.080
This record's URL: https://www.repository.cam.ac.uk/handle/1810/291223
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