Paul A Ney1. 1. Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. paul.ney@stjude.org
Abstract
PURPOSE OF REVIEW: Expression profiling is a powerful technique to sample cell state. This review shows how expression profiling is being applied to the study of erythroid differentiation. RECENT FINDINGS: Expression-based studies of multipotential hematopoietic progenitor cells has shown that these cells express lineage-restricted genes from multiple lineages at low levels, and that they are in effect 'primed' to develop into all hematopoietic cell types. Expression profiling of oligopotent and committed progenitor cells has further shown that commitment to the erythroid lineage is associated with a progressive decline in the number of expressed genes. Lineage commitment is regulated by lineage-restricted transcription factors, and studies show that the erythroid transcription factor GATA1, in addition to activating a subset of genes, has global repressive effects on gene expression. Terminal erythroid differentiation is associated with further reduction in the number of expressed genes. The erythroid program is defined by those genes that are still expressed, and their high-level expression depends on specific epigenetic modifications, recruitment of transcription factors, and posttranscriptional effects. SUMMARY: Expression profiling provides the means to identify novel targets for the therapy of erythrocytes disorders, and to obtain insights into the mechanisms of cellular differentiation.
PURPOSE OF REVIEW: Expression profiling is a powerful technique to sample cell state. This review shows how expression profiling is being applied to the study of erythroid differentiation. RECENT FINDINGS: Expression-based studies of multipotential hematopoietic progenitor cells has shown that these cells express lineage-restricted genes from multiple lineages at low levels, and that they are in effect 'primed' to develop into all hematopoietic cell types. Expression profiling of oligopotent and committed progenitor cells has further shown that commitment to the erythroid lineage is associated with a progressive decline in the number of expressed genes. Lineage commitment is regulated by lineage-restricted transcription factors, and studies show that the erythroid transcription factor GATA1, in addition to activating a subset of genes, has global repressive effects on gene expression. Terminal erythroid differentiation is associated with further reduction in the number of expressed genes. The erythroid program is defined by those genes that are still expressed, and their high-level expression depends on specific epigenetic modifications, recruitment of transcription factors, and posttranscriptional effects. SUMMARY: Expression profiling provides the means to identify novel targets for the therapy of erythrocytes disorders, and to obtain insights into the mechanisms of cellular differentiation.
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