Transcription factor-mediated lineage switching reveals plasticity in primary committed progenitor cells.

2.50
Hdl Handle:
http://hdl.handle.net/10541/82438
Title:
Transcription factor-mediated lineage switching reveals plasticity in primary committed progenitor cells.
Authors:
Heyworth, Clare M; Pearson, Stella; May, Gillian; Enver, Tariq
Abstract:
The developmental plasticity of transplanted adult stem cells challenges the notion that tissue-restricted stem cells have stringently limited lineage potential and prompts a re-evaluation of the stability of lineage commitment. Transformed cell systems are inappropriate for such studies, since transformation potentially dysregulates the processes governing lineage commitment. We have therefore assessed the stability of normal lineage commitment in primary adult haematopoietic cells. For these studies we have used prospectively isolated primary bipotent progenitors, which normally display only neutrophil and monocyte differentiation in vitro. In response to ectopic transcription factor expression, these neutrophil/monocyte progenitors were reprogrammed to take on erythroid, eosinophil and basophil-like cell fates, with the resultant colonies resembling the mixed lineage colonies normally generated by multipotential progenitors. Clone-marking and daughter cell experiments identified lineage switching rather than differential cell selection as the mechanism of altered lineage output. These results demonstrate that the cell type-specific programming of apparently committed primary progenitors is not irrevocably fixed, but may be radically re-specified in response to a single transcriptional regulator.
Affiliation:
Section of Gene Function and Regulation, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, UK.
Citation:
Transcription factor-mediated lineage switching reveals plasticity in primary committed progenitor cells. 2002, 21 (14):3770-81 EMBO J.
Journal:
The EMBO Journal
Issue Date:
15-Jul-2002
URI:
http://hdl.handle.net/10541/82438
DOI:
10.1093/emboj/cdf368
PubMed ID:
12110589
Type:
Article
Language:
en
ISSN:
0261-4189
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorHeyworth, Clare M-
dc.contributor.authorPearson, Stella-
dc.contributor.authorMay, Gillian-
dc.contributor.authorEnver, Tariq-
dc.date.accessioned2009-09-24T08:59:43Z-
dc.date.available2009-09-24T08:59:43Z-
dc.date.issued2002-07-15-
dc.identifier.citationTranscription factor-mediated lineage switching reveals plasticity in primary committed progenitor cells. 2002, 21 (14):3770-81 EMBO J.en
dc.identifier.issn0261-4189-
dc.identifier.pmid12110589-
dc.identifier.doi10.1093/emboj/cdf368-
dc.identifier.urihttp://hdl.handle.net/10541/82438-
dc.description.abstractThe developmental plasticity of transplanted adult stem cells challenges the notion that tissue-restricted stem cells have stringently limited lineage potential and prompts a re-evaluation of the stability of lineage commitment. Transformed cell systems are inappropriate for such studies, since transformation potentially dysregulates the processes governing lineage commitment. We have therefore assessed the stability of normal lineage commitment in primary adult haematopoietic cells. For these studies we have used prospectively isolated primary bipotent progenitors, which normally display only neutrophil and monocyte differentiation in vitro. In response to ectopic transcription factor expression, these neutrophil/monocyte progenitors were reprogrammed to take on erythroid, eosinophil and basophil-like cell fates, with the resultant colonies resembling the mixed lineage colonies normally generated by multipotential progenitors. Clone-marking and daughter cell experiments identified lineage switching rather than differential cell selection as the mechanism of altered lineage output. These results demonstrate that the cell type-specific programming of apparently committed primary progenitors is not irrevocably fixed, but may be radically re-specified in response to a single transcriptional regulator.en
dc.language.isoenen
dc.subject.meshBlotting, Northern-
dc.subject.meshBlotting, Western-
dc.subject.meshCell Lineage-
dc.subject.meshCytokines-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshErythroid-Specific DNA-Binding Factors-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.subject.meshStem Cells-
dc.subject.meshTranscription Factors-
dc.titleTranscription factor-mediated lineage switching reveals plasticity in primary committed progenitor cells.en
dc.typeArticleen
dc.contributor.departmentSection of Gene Function and Regulation, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, UK.en
dc.identifier.journalThe EMBO Journalen

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