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Musashi-2 controls cell fate, lineage bias, and TGF-β signaling in HSCs

Hematopoietic stem cells (HSCs) are maintained through the regulation of symmetric and asymmetric cell division. We report that conditional ablation of the RNA-binding protein Msi2 results in a failure of HSC maintenance and engraftment caused by a loss of quiescence and increased commitment divisio...

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Autores principales: Park, Sun-Mi, Deering, Raquel P., Lu, Yuheng, Tivnan, Patrick, Lianoglou, Steve, Al-Shahrour, Fatima, Ebert, Benjamin L., Hacohen, Nir, Leslie, Christina, Daley, George Q., Lengner, Christopher J., Kharas, Michael G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3892968/
https://www.ncbi.nlm.nih.gov/pubmed/24395885
http://dx.doi.org/10.1084/jem.20130736
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author Park, Sun-Mi
Deering, Raquel P.
Lu, Yuheng
Tivnan, Patrick
Lianoglou, Steve
Al-Shahrour, Fatima
Ebert, Benjamin L.
Hacohen, Nir
Leslie, Christina
Daley, George Q.
Lengner, Christopher J.
Kharas, Michael G.
author_facet Park, Sun-Mi
Deering, Raquel P.
Lu, Yuheng
Tivnan, Patrick
Lianoglou, Steve
Al-Shahrour, Fatima
Ebert, Benjamin L.
Hacohen, Nir
Leslie, Christina
Daley, George Q.
Lengner, Christopher J.
Kharas, Michael G.
author_sort Park, Sun-Mi
collection PubMed
description Hematopoietic stem cells (HSCs) are maintained through the regulation of symmetric and asymmetric cell division. We report that conditional ablation of the RNA-binding protein Msi2 results in a failure of HSC maintenance and engraftment caused by a loss of quiescence and increased commitment divisions. Contrary to previous studies, we found that these phenotypes were independent of Numb. Global transcriptome profiling and RNA target analysis uncovered Msi2 interactions at multiple nodes within pathways that govern RNA translation, stem cell function, and TGF-β signaling. Msi2-null HSCs are insensitive to TGF-β–mediated expansion and have decreased signaling output, resulting in a loss of myeloid-restricted HSCs and myeloid reconstitution. Thus, Msi2 is an important regulator of the HSC translatome and balances HSC homeostasis and lineage bias.
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spelling pubmed-38929682014-07-13 Musashi-2 controls cell fate, lineage bias, and TGF-β signaling in HSCs Park, Sun-Mi Deering, Raquel P. Lu, Yuheng Tivnan, Patrick Lianoglou, Steve Al-Shahrour, Fatima Ebert, Benjamin L. Hacohen, Nir Leslie, Christina Daley, George Q. Lengner, Christopher J. Kharas, Michael G. J Exp Med Article Hematopoietic stem cells (HSCs) are maintained through the regulation of symmetric and asymmetric cell division. We report that conditional ablation of the RNA-binding protein Msi2 results in a failure of HSC maintenance and engraftment caused by a loss of quiescence and increased commitment divisions. Contrary to previous studies, we found that these phenotypes were independent of Numb. Global transcriptome profiling and RNA target analysis uncovered Msi2 interactions at multiple nodes within pathways that govern RNA translation, stem cell function, and TGF-β signaling. Msi2-null HSCs are insensitive to TGF-β–mediated expansion and have decreased signaling output, resulting in a loss of myeloid-restricted HSCs and myeloid reconstitution. Thus, Msi2 is an important regulator of the HSC translatome and balances HSC homeostasis and lineage bias. The Rockefeller University Press 2014-01-13 /pmc/articles/PMC3892968/ /pubmed/24395885 http://dx.doi.org/10.1084/jem.20130736 Text en © 2014 Park et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Park, Sun-Mi
Deering, Raquel P.
Lu, Yuheng
Tivnan, Patrick
Lianoglou, Steve
Al-Shahrour, Fatima
Ebert, Benjamin L.
Hacohen, Nir
Leslie, Christina
Daley, George Q.
Lengner, Christopher J.
Kharas, Michael G.
Musashi-2 controls cell fate, lineage bias, and TGF-β signaling in HSCs
title Musashi-2 controls cell fate, lineage bias, and TGF-β signaling in HSCs
title_full Musashi-2 controls cell fate, lineage bias, and TGF-β signaling in HSCs
title_fullStr Musashi-2 controls cell fate, lineage bias, and TGF-β signaling in HSCs
title_full_unstemmed Musashi-2 controls cell fate, lineage bias, and TGF-β signaling in HSCs
title_short Musashi-2 controls cell fate, lineage bias, and TGF-β signaling in HSCs
title_sort musashi-2 controls cell fate, lineage bias, and tgf-β signaling in hscs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3892968/
https://www.ncbi.nlm.nih.gov/pubmed/24395885
http://dx.doi.org/10.1084/jem.20130736
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