Dr Peter Rugg - Gunn, group leader in the Babraham Institute's Epigenetics research programme and a senior co-author on the paper, explains: «One
of the exciting aspects
of this study is that we were able to capture naïve stem cells at a very early stage
of their reprogramming — these early cells had switched on a
subset of naïve -
specific genes, but they had not yet fully matured.
These mutant kinases are attractive therapeutic targets, as demonstrated by the efficacy
of imatinib in BCR - ABL — positive chronic myelogenous leukemia (CML), 5 as well as in MPD associated with activating alleles involving PDGFRA or PDGFRB.2, 6,7 In addition, activating mutations in the FLT3 receptor tyrosine kinase are the most common genetic event in acute myeloid leukemia (AML), and
specific inhibitors
of the FMS - like tyrosine kinase 3 (FLT3) have entered late - stage clinical trials.8 Although mutations in tyrosine kinases and in other
genes have been identified in a
subset of MPD and AML, in many cases the genetic events that contribute to the molecular pathogenesis
of these diseases remain unknown.
These include: a) Global Clusters that consist
of a small, tight
subset of genes that are co-expressed under the entire spectrum
of experimental conditions; b) Time Series
of gene expression profiles during successive days of standard ES cell differentiation; c) Specific Gene Classes based on hierarchical clustering of transcriptional factors and ESTs; d) Expression Waves of genes with characteristic expression profiles during ES cell differentiation, juxtaposed to waves of genes that behave in the exact opposite way; e) Pathway Animations that illustrate dynamic changes in the components of individual KEGG signaling and metabolic pathways viewed in time - related manner; and, f) Search Engines to display the expression pattern of any transcript, or groups of transcripts, during the course of ES cell differentiation, or to query the association of candidate genes with various FunGenES database clust
gene expression profiles during successive days
of standard ES cell differentiation; c)
Specific Gene Classes based on hierarchical clustering of transcriptional factors and ESTs; d) Expression Waves of genes with characteristic expression profiles during ES cell differentiation, juxtaposed to waves of genes that behave in the exact opposite way; e) Pathway Animations that illustrate dynamic changes in the components of individual KEGG signaling and metabolic pathways viewed in time - related manner; and, f) Search Engines to display the expression pattern of any transcript, or groups of transcripts, during the course of ES cell differentiation, or to query the association of candidate genes with various FunGenES database clust
Gene Classes based on hierarchical clustering
of transcriptional factors and ESTs; d) Expression Waves
of genes with characteristic expression profiles during ES cell differentiation, juxtaposed to waves
of genes that behave in the exact opposite way; e) Pathway Animations that illustrate dynamic changes in the components
of individual KEGG signaling and metabolic pathways viewed in time - related manner; and, f) Search Engines to display the expression pattern
of any transcript, or groups
of transcripts, during the course
of ES cell differentiation, or to query the association
of candidate
genes with various FunGenES database clusters.