GATA-3 REGULATES THE SELF-RENEWAL OF LONG-TERM HEMATOPOIETIC STEM CELLS

Gata3 is expressed and required for differentiation and function throughout the T lymphocyte lineage. Despite evidence it may also be expressed in multipotent hematopoietic stem cells (HSC), any role in these cells has remained unclear. Here we show GATA3 was cytoplasmic in quiescent long-term stem...

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Autores principales: Frelin, Catherine, Herrington, Robert, Janmohamed, Salima, Barbara, Mary, Tran, Gary, Paige, Christopher J., Benveniste, Patricia, Zuñiga-Pflücker, Juan-Carlos, Souabni, Abdallah, Busslinger, Meinrad, Iscove, Norman N
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972578/
https://www.ncbi.nlm.nih.gov/pubmed/23974957
http://dx.doi.org/10.1038/ni.2692
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author Frelin, Catherine
Herrington, Robert
Janmohamed, Salima
Barbara, Mary
Tran, Gary
Paige, Christopher J.
Benveniste, Patricia
Zuñiga-Pflücker, Juan-Carlos
Souabni, Abdallah
Busslinger, Meinrad
Iscove, Norman N
author_facet Frelin, Catherine
Herrington, Robert
Janmohamed, Salima
Barbara, Mary
Tran, Gary
Paige, Christopher J.
Benveniste, Patricia
Zuñiga-Pflücker, Juan-Carlos
Souabni, Abdallah
Busslinger, Meinrad
Iscove, Norman N
author_sort Frelin, Catherine
collection PubMed
description Gata3 is expressed and required for differentiation and function throughout the T lymphocyte lineage. Despite evidence it may also be expressed in multipotent hematopoietic stem cells (HSC), any role in these cells has remained unclear. Here we show GATA3 was cytoplasmic in quiescent long-term stem cells from steady state bone marrow, but relocated to the nucleus when HSC cycle. Relocation depended on p38-MAPK signaling and was associated with diminished capacity for long-term reconstitution upon transfer to irradiated mice. Deletion of Gata3 enhanced repopulating capacity and augmented self-renewal of long term HSC in cell-autonomous fashion, without affecting cell cycle. These observations position Gata3 as a regulator of the balance between self-renewal and differentiation in HSC acting downstream of the p38 signaling pathway.
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spelling pubmed-49725782016-08-03 GATA-3 REGULATES THE SELF-RENEWAL OF LONG-TERM HEMATOPOIETIC STEM CELLS Frelin, Catherine Herrington, Robert Janmohamed, Salima Barbara, Mary Tran, Gary Paige, Christopher J. Benveniste, Patricia Zuñiga-Pflücker, Juan-Carlos Souabni, Abdallah Busslinger, Meinrad Iscove, Norman N Nat Immunol Article Gata3 is expressed and required for differentiation and function throughout the T lymphocyte lineage. Despite evidence it may also be expressed in multipotent hematopoietic stem cells (HSC), any role in these cells has remained unclear. Here we show GATA3 was cytoplasmic in quiescent long-term stem cells from steady state bone marrow, but relocated to the nucleus when HSC cycle. Relocation depended on p38-MAPK signaling and was associated with diminished capacity for long-term reconstitution upon transfer to irradiated mice. Deletion of Gata3 enhanced repopulating capacity and augmented self-renewal of long term HSC in cell-autonomous fashion, without affecting cell cycle. These observations position Gata3 as a regulator of the balance between self-renewal and differentiation in HSC acting downstream of the p38 signaling pathway. 2013-08-25 2013-10 /pmc/articles/PMC4972578/ /pubmed/23974957 http://dx.doi.org/10.1038/ni.2692 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Frelin, Catherine
Herrington, Robert
Janmohamed, Salima
Barbara, Mary
Tran, Gary
Paige, Christopher J.
Benveniste, Patricia
Zuñiga-Pflücker, Juan-Carlos
Souabni, Abdallah
Busslinger, Meinrad
Iscove, Norman N
GATA-3 REGULATES THE SELF-RENEWAL OF LONG-TERM HEMATOPOIETIC STEM CELLS
title GATA-3 REGULATES THE SELF-RENEWAL OF LONG-TERM HEMATOPOIETIC STEM CELLS
title_full GATA-3 REGULATES THE SELF-RENEWAL OF LONG-TERM HEMATOPOIETIC STEM CELLS
title_fullStr GATA-3 REGULATES THE SELF-RENEWAL OF LONG-TERM HEMATOPOIETIC STEM CELLS
title_full_unstemmed GATA-3 REGULATES THE SELF-RENEWAL OF LONG-TERM HEMATOPOIETIC STEM CELLS
title_short GATA-3 REGULATES THE SELF-RENEWAL OF LONG-TERM HEMATOPOIETIC STEM CELLS
title_sort gata-3 regulates the self-renewal of long-term hematopoietic stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972578/
https://www.ncbi.nlm.nih.gov/pubmed/23974957
http://dx.doi.org/10.1038/ni.2692
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