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Determining c-Myb protein levels can isolate functional hematopoietic stem cell subtypes.
Sakamoto, Hiroshi; Takeda, Naoki; Arai, Fumio; Hosokawa, Kentaro; Garcia, Paloma; Suda, Toshio; Frampton, Jon; Ogawa, Minetaro.
Afiliação
  • Sakamoto H; Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto City, Japan.
Stem Cells ; 33(2): 479-90, 2015 Feb.
Article em En | MEDLINE | ID: mdl-25329760
ABSTRACT
The transcription factor c-Myb was originally identified as a transforming oncoprotein encoded by two avian leukemia viruses. Subsequently, through the generation of mouse models that affect its expression, c-Myb has been shown to be a key regulator of hematopoiesis, including having critical roles in hematopoietic stem cells (HSCs). The precise function of c-Myb in HSCs although remains unclear. We have generated a novel c-myb allele in mice that allows direct observation of c-Myb protein levels in single cells. Using this reporter line we demonstrate that subtypes of HSCs can be isolated based upon their respective c-Myb protein expression levels. HSCs expressing low levels of c-Myb protein (c-Myb(low) HSC) appear to represent the most immature, dormant HSCs and they are a predominant component of HSCs that retain bromodeoxyuridine labeling. Hematopoietic stress, induced by 5-fluorouracil ablation, revealed that in this circumstance c-Myb-expressing cells become critical for multilineage repopulation. The discrimination of HSC subpopulations based on c-Myb protein levels is not reflected in the levels of c-myb mRNA, there being no more than a 1.3-fold difference comparing c-Myb(low) and c-Myb(high) HSCs. This illustrates how essential it is to include protein studies when aiming to understand the regulatory networks that control stem cell behavior.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células-Tronco Hematopoéticas / Regulação da Expressão Gênica / Proteínas Proto-Oncogênicas c-myb / Hematopoese Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células-Tronco Hematopoéticas / Regulação da Expressão Gênica / Proteínas Proto-Oncogênicas c-myb / Hematopoese Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2015 Tipo de documento: Article