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lncRNA Spehd Regulates Hematopoietic Stem and Progenitor Cells and Is Required for Multilineage Differentiation.

Accepted version
Peer-reviewed

Type

Article

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Authors

Delás, M Joaquina 
Jackson, Benjamin T 
Kovacevic, Tatjana 
Vangelisti, Silvia 
Munera Maravilla, Ester 

Abstract

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 may 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 multilineage differentiation, and its silencing yielded common myeloid progenitors that are 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.

Description

Keywords

HSC, hematopoiesis, lncRNA, oxidative phosphorylation, Animals, Bone Marrow Transplantation, Cell Differentiation, Cell Line, Tumor, Cell Lineage, Cyclin-Dependent Kinase 6, Female, GATA2 Transcription Factor, Hematopoiesis, Hematopoietic Stem Cells, Mice, Mice, Inbred C57BL, Oxidative Phosphorylation, Proto-Oncogene Proteins, RNA Interference, RNA, Long Noncoding, RNA, Small Interfering, Regeneration, Trans-Activators

Journal Title

Cell Rep

Conference Name

Journal ISSN

2211-1247
2211-1247

Volume Title

27

Publisher

Elsevier BV

Rights

All rights reserved
Sponsorship
Cancer Research UK (C14303/A17197)
Wellcome Trust (110161/Z/15/Z)
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.