Reduced c-Myb activity compromises HSCs and leads to a myeloproliferation with a novel stem cell basis.

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Reduced c-Myb activity compromises HSCs and leads to a myeloproliferation with a novel stem cell basis. / Garcia, Paloma; Clarke, Mary; Vegiopoulos, A; Berlanga, Oscar; Camelo, A; Lorvellec, Maelle; Frampton, Jonathan.

In: The EMBO journal, Vol. 28, No. 10, 20.05.2009, p. 1492-504.

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@article{1c66ead4cd4746f29cea01598402290c,
title = "Reduced c-Myb activity compromises HSCs and leads to a myeloproliferation with a novel stem cell basis.",
abstract = "Murine haematopoietic stem cells (HSCs) are contained in the Kit+Sca1+Lin(-) (KSL) population of bone marrow and are able to repopulate lethally irradiated mice. Myeloproliferative disorders (MPDs) are thought to be clonogenic diseases arising at the level of the HSC. Here, we show that mice expressing low levels of the transcription factor c-Myb, as the result of genetic knockdown, develop a transplantable myeloproliferative phenotype that closely resembles the human disease essential thrombocythaemia (ET). Unlike wild-type cells, the KSL population in c-myb knockdown bone marrow cannot repopulate irradiated mice and does not transfer the disease. Instead, cells positive for Kit and expressing low to medium levels of CD11b acquire self-renewing stem cell properties and are responsible for the perpetuation of the myeloproliferative phenotype.",
keywords = "myeloproliferative disorder, differentiation commitment, haematopoietic stem cell, self-renewal, c-Myb",
author = "Paloma Garcia and Mary Clarke and A Vegiopoulos and Oscar Berlanga and A Camelo and Maelle Lorvellec and Jonathan Frampton",
year = "2009",
month = may,
day = "20",
doi = "10.1038/emboj.2009.97",
language = "English",
volume = "28",
pages = "1492--504",
journal = "The EMBO journal",
issn = "0261-4189",
publisher = "EMBO Press",
number = "10",

}

RIS

TY - JOUR

T1 - Reduced c-Myb activity compromises HSCs and leads to a myeloproliferation with a novel stem cell basis.

AU - Garcia, Paloma

AU - Clarke, Mary

AU - Vegiopoulos, A

AU - Berlanga, Oscar

AU - Camelo, A

AU - Lorvellec, Maelle

AU - Frampton, Jonathan

PY - 2009/5/20

Y1 - 2009/5/20

N2 - Murine haematopoietic stem cells (HSCs) are contained in the Kit+Sca1+Lin(-) (KSL) population of bone marrow and are able to repopulate lethally irradiated mice. Myeloproliferative disorders (MPDs) are thought to be clonogenic diseases arising at the level of the HSC. Here, we show that mice expressing low levels of the transcription factor c-Myb, as the result of genetic knockdown, develop a transplantable myeloproliferative phenotype that closely resembles the human disease essential thrombocythaemia (ET). Unlike wild-type cells, the KSL population in c-myb knockdown bone marrow cannot repopulate irradiated mice and does not transfer the disease. Instead, cells positive for Kit and expressing low to medium levels of CD11b acquire self-renewing stem cell properties and are responsible for the perpetuation of the myeloproliferative phenotype.

AB - Murine haematopoietic stem cells (HSCs) are contained in the Kit+Sca1+Lin(-) (KSL) population of bone marrow and are able to repopulate lethally irradiated mice. Myeloproliferative disorders (MPDs) are thought to be clonogenic diseases arising at the level of the HSC. Here, we show that mice expressing low levels of the transcription factor c-Myb, as the result of genetic knockdown, develop a transplantable myeloproliferative phenotype that closely resembles the human disease essential thrombocythaemia (ET). Unlike wild-type cells, the KSL population in c-myb knockdown bone marrow cannot repopulate irradiated mice and does not transfer the disease. Instead, cells positive for Kit and expressing low to medium levels of CD11b acquire self-renewing stem cell properties and are responsible for the perpetuation of the myeloproliferative phenotype.

KW - myeloproliferative disorder

KW - differentiation commitment

KW - haematopoietic stem cell

KW - self-renewal

KW - c-Myb

U2 - 10.1038/emboj.2009.97

DO - 10.1038/emboj.2009.97

M3 - Article

C2 - 19360001

VL - 28

SP - 1492

EP - 1504

JO - The EMBO journal

JF - The EMBO journal

SN - 0261-4189

IS - 10

ER -