Expression map of the human exome in CD34+ cells and blood cells: increased alternative splicing in cell motility and immune response genes

• Published in: PloS one 2010-02, Vol.5 (2), p.e8990-e8990
• Main Authors: Tondeur, Sylvie, Pangault, Céline, Le Carrour, Tanguy, Lannay, Yoann, Benmahdi, Rima, Cubizolle, Aurélie, Assou, Said, Pantesco, Véronique, Klein, Bernard, Hamamah, Samir, Schved, Jean-François, Fest, Thierry, De Vos, John
• Format: Article
• Language: English
• Subjects: Algorithms; Alternative splicing; Alternative Splicing - genetics; Antigens, CD34 - blood; B cells; Biochemistry, Molecular Biology; Blood; Blood cells; Blood Cells - cytology; Blood Cells - metabolism; Bone marrow; Brain cancer; Breast - metabolism; Breast cancer; CD14 antigen; CD19 antigen; CD3 antigen; CD34 antigen; Cell adhesion; Cell differentiation; Cell Movement - genetics; Cells (biology); Colorectal cancer; Computational Biology/Alternative Splicing; Differentiation (biology); Disease control; Erythrocytes; Exons - genetics; Female; Gene expression; Gene Expression Profiling; Genes; Genetic engineering; Genetics; Genetics and Genomics/Gene Expression; Genomes; Genomics; Hematology; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Humans; Immune response; Immune system; Immunity - genetics; Inflammation; Kidney - metabolism; Life Sciences; Ligands; Liver - metabolism; Lymphocytes; Lymphocytes B; Lymphocytes T; Male; Metastasis; Motility; Mutation; Oligonucleotide Array Sequence Analysis - methods; Organs; Osteoprogenitor cells; Platelets; Pluripotency; Principal Component Analysis; Prostate - metabolism; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Stem cells; T cells; Tissues; Transcription; Trends; Tumors; Wounding
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0008990

Hematopoietic cells are endowed with very specific biological functions, including cell motility and immune response. These specific functions are dramatically altered during hematopoietic cell differentiation, whereby undifferentiated hematopoietic stem and progenitor cells (HSPC) residing in bone marrow differentiate into platelets, red blood cells and immune cells that exit into the blood stream and eventually move into lymphoid organs or inflamed tissues. The contribution of alternative splicing (AS) to these functions has long been minimized due to incomplete knowledge on AS events in hematopoietic cells. Using Human Exon ST 1.0 microarrays, the entire exome expression profile of immature CD34+ HSPC and mature whole blood cells was mapped, compared to a collection of solid tissues and made freely available as an online exome expression atlas (Amazonia Exon! : http://amazonia.transcriptome.eu/exon.php). At a whole transcript level, HSPC strongly expressed EREG and the pluripotency marker DPPA4. Using a differential splicing index scheme (dsi), a list of 849 transcripts differentially expressed between hematopoietic cells and solid tissues was computed, that included NEDD9 and CD74. Some of these genes also underwent alternative splicing events during hematopoietic differentiation, such as INPP4B, PTPLA or COMMD6, with varied contribution of CD3+ T cells, CD19+ B cells, CD14+ or CD15+ myelomonocytic populations. Strikingly, these genes were significantly enriched for genes involved in cell motility, cell adhesion, response to wounding and immune processes. The relevance and the precision provided by this exon expression map highlights the contribution of alternative splicing to key feature of blood cells differentiation and function.