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


RESULTS
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.


CONCLUSIONS
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.
Tondeur
Sylvie
S
CHU Montpellier, Institute for Research in Biotherapy, Hôpital Saint-Eloi, Montpellier, France.
Pangault
Céline
C
Le Carrour
Tanguy
T
Lannay
Yoann
Y
Benmahdi
Rima
R
Cubizolle
Aurélie
A
Assou
Said
S
Pantesco
Véronique
V
Klein
Bernard
B
Hamamah
Samir
S
Schved
Jean-François
JF
Fest
Thierry
T
De Vos
John
J
D000465:Algorithms; D017398:Alternative Splicing / Q000235:genetics; D018952:Antigens, CD34 / Q000097:blood; D001773:Blood Cells / Q000166:cytology / Q000378:metabolism*; D001940:Breast / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D005091:Exons / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007109:Immunity / Q000235:genetics; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D025341:Principal Component Analysis; D011467:Prostate / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018952:Antigens, CD34