Transcriptional profiling of hematopoietic cell subpopulations has helped to characterize the developmental stages of the hematopoietic system and the molecular bases of malignant and non-malignant blood diseases. Previously, only the genes targeted by expression microarrays could be profiled genome-wide. High-throughput RNA sequencing, however, encompasses a broader repertoire of RNA molecules, without restriction to previously annotated genes. We analyzed the BLUEPRINT consortium RNA-sequencing data for mature hematopoietic cell types. The data comprised 90 total RNA-sequencing samples, each composed of one of 27 cell types, and 32 small RNA-sequencing 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 RNA 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 hematologic development and diseases. Finally, we made the data accessible via a web-based interface: https://blueprint.haem.cam.ac.uk/bloodatlas/.The authors would like to acknowledge the participation of National Institute of Health
Research (NIHR) Cambridge BioResource volunteers and thank the NIHR Cambridge
BioResource staff for their support. The work was funded by a grant from the European
Commission 7th Framework Program (FP7/2007–2013, grant 282510, BLUEPRINT)
to XE, PF, JHAM, MY, HGS and WHO. WHO is an NIHR senior investigator and
receives funding from Bristol-Myers Squibb, the British Heart Foundation, the Medical
Research Council and the NIHR. OGI, FJM, AF, JMM, LC and PF are funded by the
Wellcome Trust (WT108749/Z/15/Z) with additional funding for specific project
components such as GENCODE from the National Human Genome Research
Institute of the National Institutes of Health (2U41HG007234), accordingly the content
of this manuscript is solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health. KD is a HSST trainee
supported by NHS Health Education England. NF is funded by the NIHR Cambridge
Biomedical Research Centre. FP is supported by the Fundação Carlos Chagas Filho
de Amparo à Pesquisado Estado do Rio de Janeiro (FAPERJ; E-26/203.229/2016).
NANJ is a recipient of a scholarship from the Coordenação de Aperfeiçoamento de
Pessoal de Nível Superior - Brasil (CAPES; Finance Code 001). DS work has been
supported in part by an Isaac Newton fellowship to MF. MF is supported by the British
Heart Foundation (FS/18/53/33863)