E-MTAB-1452 - Transcription profiling by array of pure populations of human megakaryocytes (MK) derived from embryonic stem cells (MKES), fetal liver (MKFL), cord blood (MKCB) and adult blood (MKAD)
Released on 24 June 2013, last updated on 3 May 2014
The molecular bases of cellular changes that occur during ontogeny of human megakaryopoiesis remained unknown. We performed global gene expression profiling of pure populations of megakaryocytes (MK) derived from ES cells (MKES), fetal liver (MKFL), cord blood (MKCB) and adult blood (MKAD). A close pair-wise relationship between MKES and MKFL and between MKCB and MKAD was detected, respectively. A modest number of genes (695) was found differentially regulated along development. Major changes occurred in genes encoding cytoskeleton, platelet membrane and a-granule proteins, suggesting a functional MK maturation during development. MK ontogeny-associated changes in the expression of cell cycle regulators (e.g. AURKA, AURKB, PLK1) may account for the progressive increase in cell ploidy observed all along ontogeny. Several genes, including lin28B, were specific for embryonic and fetal MK whereas others, like CXCR4, were specific of the neonate and adult stage. In accordance with the absence of CXCR4 expression in embryonic MK, their migration was independent of SDF1, which functionally validates the changes in gene expression. Finally, the pattern of transcription factor network and signaling pathways (GATA1, SRF, MYC and Notch pathway) was consistent with the hypothesis that de novo acute megakaryoblastic leukemia, which predominantly affects children, develop from early MK. This transcriptomic analysis is dedicated to identify genes that are diffentially expressed during human megakaryocyte ontogeny. To that purpose, several samples of MK were differentiated from human embryonic stem cell lines (MKES1 to MKES4), from CD34 positives cells of fetal liver (MKFL1 to MKFL3), of cord blood (MKCB1 to MKCB3) or from adult blood (MKAD1 to MKAD3). These samples were hybridized in dual color and dye-swap on 8x60K Agilent whole genome human array (design 028004).
transcription profiling by array, co-expression, development or differentiation, dye swap, reference, replicate