期刊
STEM CELLS
卷 33, 期 2, 页码 479-490出版社
WILEY-BLACKWELL
DOI: 10.1002/stem.1855
关键词
Hematopoietic stem cells; Proto-oncogene proteins c-myb; Animals; Genetically modified; Hematopoietic stem cell transplantation; Cell proliferation; Hematopoiesis
资金
- KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan [19591120, 21591208, 24591400]
- Japan Science and Technology Agency, CREST
- JSPS
- Leukemia and Lymphoma Research
- MRC [MR/K01076X/1, G0501688] Funding Source: UKRI
- Medical Research Council [G0501688, MR/K01076X/1] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [21591208, 26670471, 221S0001, 26293228, 24591400, 19591120] Funding Source: KAKEN
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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