miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells

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To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample L...

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Autores principales: Lechman, Eric R., Gentner, Bernhard, Ng, Stanley W.K., Schoof, Erwin M., van Galen, Peter, Kennedy, James A., Nucera, Silvia, Ciceri, Fabio, Kaufmann, Kerstin B., Takayama, Naoya, Dobson, Stephanie M., Trotman-Grant, Aaron, Krivdova, Gabriela, Elzinga, Janneke, Mitchell, Amanda, Nilsson, Björn, Hermans, Karin G., Eppert, Kolja, Marke, Rene, Isserlin, Ruth, Voisin, Veronique, Bader, Gary D., Zandstra, Peter W., Golub, Todd R., Ebert, Benjamin L., Lu, Jun, Minden, Mark, Wang, Jean C.Y., Naldini, Luigi, Dick, John E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749543/
https://www.ncbi.nlm.nih.gov/pubmed/26832662
http://dx.doi.org/10.1016/j.ccell.2015.12.011
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author Lechman, Eric R.
Gentner, Bernhard
Ng, Stanley W.K.
Schoof, Erwin M.
van Galen, Peter
Kennedy, James A.
Nucera, Silvia
Ciceri, Fabio
Kaufmann, Kerstin B.
Takayama, Naoya
Dobson, Stephanie M.
Trotman-Grant, Aaron
Krivdova, Gabriela
Elzinga, Janneke
Mitchell, Amanda
Nilsson, Björn
Hermans, Karin G.
Eppert, Kolja
Marke, Rene
Isserlin, Ruth
Voisin, Veronique
Bader, Gary D.
Zandstra, Peter W.
Golub, Todd R.
Ebert, Benjamin L.
Lu, Jun
Minden, Mark
Wang, Jean C.Y.
Naldini, Luigi
Dick, John E.
author_facet Lechman, Eric R.
Gentner, Bernhard
Ng, Stanley W.K.
Schoof, Erwin M.
van Galen, Peter
Kennedy, James A.
Nucera, Silvia
Ciceri, Fabio
Kaufmann, Kerstin B.
Takayama, Naoya
Dobson, Stephanie M.
Trotman-Grant, Aaron
Krivdova, Gabriela
Elzinga, Janneke
Mitchell, Amanda
Nilsson, Björn
Hermans, Karin G.
Eppert, Kolja
Marke, Rene
Isserlin, Ruth
Voisin, Veronique
Bader, Gary D.
Zandstra, Peter W.
Golub, Todd R.
Ebert, Benjamin L.
Lu, Jun
Minden, Mark
Wang, Jean C.Y.
Naldini, Luigi
Dick, John E.
author_sort Lechman, Eric R.
collection PubMed
description To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and proteome analysis demonstrates that miR-126 targets the PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance.
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spelling pubmed-47495432016-02-29 miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells Lechman, Eric R. Gentner, Bernhard Ng, Stanley W.K. Schoof, Erwin M. van Galen, Peter Kennedy, James A. Nucera, Silvia Ciceri, Fabio Kaufmann, Kerstin B. Takayama, Naoya Dobson, Stephanie M. Trotman-Grant, Aaron Krivdova, Gabriela Elzinga, Janneke Mitchell, Amanda Nilsson, Björn Hermans, Karin G. Eppert, Kolja Marke, Rene Isserlin, Ruth Voisin, Veronique Bader, Gary D. Zandstra, Peter W. Golub, Todd R. Ebert, Benjamin L. Lu, Jun Minden, Mark Wang, Jean C.Y. Naldini, Luigi Dick, John E. Cancer Cell Article To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and proteome analysis demonstrates that miR-126 targets the PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance. Cell Press 2016-02-08 /pmc/articles/PMC4749543/ /pubmed/26832662 http://dx.doi.org/10.1016/j.ccell.2015.12.011 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Lechman, Eric R.
Gentner, Bernhard
Ng, Stanley W.K.
Schoof, Erwin M.
van Galen, Peter
Kennedy, James A.
Nucera, Silvia
Ciceri, Fabio
Kaufmann, Kerstin B.
Takayama, Naoya
Dobson, Stephanie M.
Trotman-Grant, Aaron
Krivdova, Gabriela
Elzinga, Janneke
Mitchell, Amanda
Nilsson, Björn
Hermans, Karin G.
Eppert, Kolja
Marke, Rene
Isserlin, Ruth
Voisin, Veronique
Bader, Gary D.
Zandstra, Peter W.
Golub, Todd R.
Ebert, Benjamin L.
Lu, Jun
Minden, Mark
Wang, Jean C.Y.
Naldini, Luigi
Dick, John E.
miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells
title miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells
title_full miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells
title_fullStr miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells
title_full_unstemmed miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells
title_short miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells
title_sort mir-126 regulates distinct self-renewal outcomes in normal and malignant hematopoietic stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749543/
https://www.ncbi.nlm.nih.gov/pubmed/26832662
http://dx.doi.org/10.1016/j.ccell.2015.12.011
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