The Contribution of lincRNAs at the Interface between Cell Cycle Regulation and Cell State Maintenance

Cell cycle progression is controlled by the interplay of established cell cycle regulators. Changes in these regulators' activity underpin differences in cell cycle kinetics between cell types. We investigated whether long intergenic noncoding RNAs (lincRNAs) contribute to embryonic stem cell cycle adaptations. Using single-cell RNA sequencing data for mouse embryonic stem cells (mESCs) staged as G1, S, or G2/M we found differentially expressed lincRNAs are enriched among cell cycle-regulated genes. These lincRNAs (CC-lincRNAs) are co-expressed with genes involved in cell cycle regulation. We tested the impact of two CC-lincRNA candidates and show using CRISPR activation that increasing their expression is associated with deregulated cell cycle progression. Interestingly, CC-lincRNAs are often differentially expressed between G1 and S, their promoters are enriched in pluripotency transcription factor (TF) binding sites, and their transcripts are frequently co-regulated with genes involved in the maintenance of pluripotency, suggesting a contribution of CC-lincRNAs to mESC cell cycle adaptations

Clinical impact of bone marrow morphology for the diagnosis of essential thrombocythemia: comparison between the BCSH and the WHO criteria

Essential thrombocythemia (ET) is currently diagnosed either by the British Committee of Standards in Haematology (BCSH) criteria that are predominantly based on exclusion and not necessarily on bone marrow (BM) morphology, or the World Health Organization (WHO) criteria that require BM examination as essential criterion. We studied the morphological and clinical features in patients diagnosed according either to the BCSH (n = 238) or the WHO guidelines (n = 232). The BCSH-defined ET cohort was reevaluated by applying the WHO classification. At presentation, patients of the BCSH group showed significantly higher values of serum lactate dehydrogenase and had palpable splenomegaly more frequently. Following the WHO criteria, the re-evaluation of the BCSH-diagnosed ET cohort displayed a heterogeneous population with 141 (59.2%) ET, 77 (32.4%) prefibrotic primary myelofibrosis (prePMF), 16 (6.7%) polycythemia vera and 4 (1.7%) primary myelofibrosis. Contrasting WHO-confirmed ET, the BCSH cohort revealed a significant worsening of fibrosis-free survival and prognosis. As demonstrated by the clinical data and different outcomes between WHO-diagnosed ET and prePMF, these adverse features were generated by the inadvertent inclusion of prePMF to the BCSH group. Taken together, the diagnosis of ET without a scrutinized examination of BM biopsy specimens will generate a heterogeneous cohort of patients impairing an appropriate clinical management