RT Journal Article SR Electronic T1 LncRNA Spehd regulates hematopoietic stem cells and progenitors and is required for multilineage differentiation JF bioRxiv FD Cold Spring Harbor Laboratory SP 340034 DO 10.1101/340034 A1 M Joaquina Delás A1 Benjamin T Jackson A1 Tatjana Kovacevic A1 Silvia Vangelisti A1 Ester Munera Maravilla A1 Sophia A Wild A1 Eva Maria Stork A1 Nicolas Erard A1 Simon RV Knott A1 Gregory J Hannon YR 2018 UL http://biorxiv.org/content/early/2018/06/14/340034.abstract AB 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.