OBJECTIVE: To identify genes involved in megakaryopoiesis, high-density oligonucleotide microarrays were used to compare transcript profiles from undifferentiated CD34+CD38lo cells and culture-derived megakaryocytes (MKs). MATERIALS AND METHODS: Megakaryocyte differentiation was achieved in vitro by inducing primary human CD34+CD38lo cells in serum-deprived media supplemented with the cytokine combination of interleukin-3, interleukin-6, stem cell factor, and thrombopoietin for 10 days. Three replicate microarray experiments were performed using hematopoietic cells isolated from three different organ donors and high-density oligonucleotide microarrays. RESULTS: Analysis of gene array data resulted in 304 differentially expressed genes (p < or = 0.001, fold change > or = 3). A third of the 25 most highly up-regulated genes were known to participate in hemostasis (z = 6.75), and no genes known to be associated with MKs were among the down-regulated genes. We also found a large proportion of up-regulated transcripts in gene ontology categories of adhesion and receptor activity (85%) and signal transduction activity (68%). At the same time, 70% of genes within transcription factor functions were down-regulated. Confirmatory studies indicated that the array results correlated with mRNA and protein expression levels in primary MKs. CONCLUSION: This study provides a global expression profile of human MKs and a list of novel and previously uncharacterized candidate genes that are important components of megakaryopoiesis.
OBJECTIVE: To identify genes involved in megakaryopoiesis, high-density oligonucleotide microarrays were used to compare transcript profiles from undifferentiated CD34+CD38lo cells and culture-derived megakaryocytes (MKs). MATERIALS AND METHODS: Megakaryocyte differentiation was achieved in vitro by inducing primary humanCD34+CD38lo cells in serum-deprived media supplemented with the cytokine combination of interleukin-3, interleukin-6, stem cell factor, and thrombopoietin for 10 days. Three replicate microarray experiments were performed using hematopoietic cells isolated from three different organ donors and high-density oligonucleotide microarrays. RESULTS: Analysis of gene array data resulted in 304 differentially expressed genes (p < or = 0.001, fold change > or = 3). A third of the 25 most highly up-regulated genes were known to participate in hemostasis (z = 6.75), and no genes known to be associated with MKs were among the down-regulated genes. We also found a large proportion of up-regulated transcripts in gene ontology categories of adhesion and receptor activity (85%) and signal transduction activity (68%). At the same time, 70% of genes within transcription factor functions were down-regulated. Confirmatory studies indicated that the array results correlated with mRNA and protein expression levels in primary MKs. CONCLUSION: This study provides a global expression profile of human MKs and a list of novel and previously uncharacterized candidate genes that are important components of megakaryopoiesis.
Authors: O I Petriv; F Kuchenbauer; A D Delaney; V Lecault; A White; D Kent; L Marmolejo; M Heuser; T Berg; M Copley; J Ruschmann; S Sekulovic; C Benz; E Kuroda; V Ho; F Antignano; T Halim; V Giambra; G Krystal; C J F Takei; A P Weng; J Piret; C Eaves; M A Marra; R K Humphries; C L Hansen Journal: Proc Natl Acad Sci U S A Date: 2010-08-11 Impact factor: 11.205
Authors: Iain C Macaulay; Philippa Carr; Arief Gusnanto; Willem H Ouwehand; Des Fitzgerald; Nicholas A Watkins Journal: J Clin Invest Date: 2005-12 Impact factor: 14.808
Authors: Minggao Liang; Asim Soomro; Subia Tasneem; Luis E Abatti; Azad Alizada; Xuefei Yuan; Liis Uusküla-Reimand; Lina Antounians; Sana Akhtar Alvi; Andrew D Paterson; Georges-Étienne Rivard; Ian C Scott; Jennifer A Mitchell; Catherine P M Hayward; Michael D Wilson Journal: Blood Date: 2020-12-03 Impact factor: 22.113