Cell type specific novel lncRNAs and circRNAs in the BLUEPRINT haematopoietic transcriptomes atlas.

Transcriptional profiling of hematopoietic cell subpopulations has helped characterize the developmental stages of the hematopoietic system and the molecular bases of malignant and non-malignant blood diseases for the past three decades. Previously, only the genes targeted by expression microarrays could be profiled genome wide. High-throughput RNA sequencing (RNA-seq), however, encompasses a broader repertoire of RNA molecules, without restriction to previously annotated genes. We analysed the BLUEPRINT consortium RNA- seq data for mature hematopoietic cell types. The data comprised 90 total RNA-seq samples, each composed of one of 27 cell types, and 32 small RNA-seq samples, each composed of one of 11 cell types. We estimated gene and isoform expression levels for each cell type using existing annotations from Ensembl. We then used guided transcriptome assembly to discover unannotated transcripts. We identified hundreds of novel non-coding RNA genes and showed that the majority have cell type dependent expression. We also characterized the expression of circular RNAs and found that these are also cell type specific. These analyses refine the active transcriptional landscape of mature hematopoietic cells, highlight abundant genes and transcriptional isoforms for each blood cell type, and provide a valuable resource for researchers of hematological development and diseases. Finally, we made the data accessible via a web-based interface: https://blueprint.haem.cam.ac.uk/bloodatlas/.