Molecular signatures of self-renewal, differentiation, and lineage choice in multipotential hemopoietic progenitor cells in vitro.

2.50
Hdl Handle:
http://hdl.handle.net/10541/78359
Title:
Molecular signatures of self-renewal, differentiation, and lineage choice in multipotential hemopoietic progenitor cells in vitro.
Authors:
Bruno, Ludovica; Hoffmann, Reinhard; McBlane, Fraser; Brown, John; Gupta, Rajeev; Joshi, Chirag; Pearson, Stella; Seidl, Thomas; Heyworth, Clare M; Enver, Tariq
Abstract:
The molecular mechanisms governing self-renewal, differentiation, and lineage specification remain unknown. Transcriptional profiling is likely to provide insight into these processes but, as yet, has been confined to "static" molecular profiles of stem and progenitors cells. We now provide a comprehensive, statistically robust, and "dynamic" analysis of multipotent hemopoietic progenitor cells undergoing self-renewal in response to interleukin-3 (IL-3) and multilineage differentiation in response to lineage-affiliated cytokines. Cells undergoing IL-3-dependent proliferative self-renewal displayed striking complexity, including expression of genes associated with different lineage programs, suggesting a highly responsive compartment poised to rapidly execute intrinsically or extrinsically initiated cell fate decisions. A remarkable general feature of early differentiation was a resolution of complexity through the downregulation of gene expression. Although effector genes characteristic of mature cells were upregulated late, coincident with morphological changes, lineage-specific changes in gene expression were observed prior to this, identifying genes which may provide early harbingers of unilineage commitment. Of particular interest were genes that displayed differential behavior irrespective of the lineage elaborated, many of which were rapidly downregulated within 4 to 8 h after exposure to a differentiation cue. These are likely to include genes important in self-renewal, the maintenance of multipotentiality, or the negative regulation of differentiation per se.
Affiliation:
Section of Gene Function and Regulation, The Institute of Cancer Research, London SW3 6JB, UK.
Citation:
Molecular signatures of self-renewal, differentiation, and lineage choice in multipotential hemopoietic progenitor cells in vitro. 2004, 24 (2):741-56 Mol. Cell. Biol.
Journal:
Molecular and Cellular Biology
Issue Date:
Jan-2004
URI:
http://hdl.handle.net/10541/78359
PubMed ID:
14701746
Type:
Article
Language:
en
ISSN:
0270-7306
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBruno, Ludovica-
dc.contributor.authorHoffmann, Reinhard-
dc.contributor.authorMcBlane, Fraser-
dc.contributor.authorBrown, John-
dc.contributor.authorGupta, Rajeev-
dc.contributor.authorJoshi, Chirag-
dc.contributor.authorPearson, Stella-
dc.contributor.authorSeidl, Thomas-
dc.contributor.authorHeyworth, Clare M-
dc.contributor.authorEnver, Tariq-
dc.date.accessioned2009-08-24T15:40:32Z-
dc.date.available2009-08-24T15:40:32Z-
dc.date.issued2004-01-
dc.identifier.citationMolecular signatures of self-renewal, differentiation, and lineage choice in multipotential hemopoietic progenitor cells in vitro. 2004, 24 (2):741-56 Mol. Cell. Biol.en
dc.identifier.issn0270-7306-
dc.identifier.pmid14701746-
dc.identifier.urihttp://hdl.handle.net/10541/78359-
dc.description.abstractThe molecular mechanisms governing self-renewal, differentiation, and lineage specification remain unknown. Transcriptional profiling is likely to provide insight into these processes but, as yet, has been confined to "static" molecular profiles of stem and progenitors cells. We now provide a comprehensive, statistically robust, and "dynamic" analysis of multipotent hemopoietic progenitor cells undergoing self-renewal in response to interleukin-3 (IL-3) and multilineage differentiation in response to lineage-affiliated cytokines. Cells undergoing IL-3-dependent proliferative self-renewal displayed striking complexity, including expression of genes associated with different lineage programs, suggesting a highly responsive compartment poised to rapidly execute intrinsically or extrinsically initiated cell fate decisions. A remarkable general feature of early differentiation was a resolution of complexity through the downregulation of gene expression. Although effector genes characteristic of mature cells were upregulated late, coincident with morphological changes, lineage-specific changes in gene expression were observed prior to this, identifying genes which may provide early harbingers of unilineage commitment. Of particular interest were genes that displayed differential behavior irrespective of the lineage elaborated, many of which were rapidly downregulated within 4 to 8 h after exposure to a differentiation cue. These are likely to include genes important in self-renewal, the maintenance of multipotentiality, or the negative regulation of differentiation per se.en
dc.language.isoenen
dc.subjectHaematopoiesisen
dc.subjectHaematopoietic Cell Growth Factorsen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshAnimals-
dc.subject.meshCell Differentiation-
dc.subject.meshCell Division-
dc.subject.meshCells, Cultured-
dc.subject.meshGene Expression Profiling-
dc.subject.meshGene Expression Regulation, Developmental-
dc.subject.meshHematopoiesis-
dc.subject.meshHematopoietic Cell Growth Factors-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshInterleukin-3-
dc.subject.meshMice-
dc.subject.meshMultipotent Stem Cells-
dc.subject.meshOligonucleotide Array Sequence Analysis-
dc.subject.meshSignal Transduction-
dc.titleMolecular signatures of self-renewal, differentiation, and lineage choice in multipotential hemopoietic progenitor cells in vitro.en
dc.typeArticleen
dc.contributor.departmentSection of Gene Function and Regulation, The Institute of Cancer Research, London SW3 6JB, UK.en
dc.identifier.journalMolecular and Cellular Biologyen

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