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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2018.1
- 수록면
- 953 - 963 (11page)
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초록· 키워드
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The stem cell factor (SCF)/c-KIT axis plays an important role in the hematopoietic differentiation of human pluripotent stem cells (hPSCs), but its regulatory mechanisms involving microRNAs (miRs) are not fully elucidated. Here, we demonstrated that supplementation with SCF increases the hematopoietic differentiation of hPSCs via the interaction with its receptor tyrosine kinase c-KIT, which is modulated by miR-221 and miR-222. c-KIT is comparably expressed in undifferentiated human embryonic and induced pluripotent stem cells. The inhibition of SCF signaling via treatment with a c-KIT antagonist (imatinib) during hPSC-derived hematopoiesis resulted in reductions in the yield and multi-lineage potential of hematopoietic progenitors. We found that the transcript levels of miR-221 and miR-222 targeting c-KIT were significantly lower in the pluripotent state than they were in terminally differentiated somatic cells. Furthermore, suppression of miR-221 and miR-222 in undifferentiated hPSC cultures induced more hematopoiesis by increasing c-KIT expression. Collectively, our data implied that the modulation of c-KIT by miRs may provide further potential strategies to expedite the generation of functional blood cells for therapeutic approaches and the study of the cellular machinery related to hematologic malignant diseases such as leukemia.
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참고문헌 (47)
참고문헌 신청
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Atamas, S. P. / 1996 / An alternative splice variant of human IL-4, IL-4 delta 2, inhibits IL-4-stimulated T cell proliferation / J. Immunol 156:435~441
Baek, S. J. / 2016 / Integrated epigenomic analyses of enhancer as well as promoter regions in gastric cancer / Oncotarget 7:25620~25631
Bernstein, B. E. / 2007 / The mammalian epigenome / Cell 128:669~681
David-Fung, E. S. / 2009 / Transcription factor expression dynamics of early T-lymphocyte specification and commitment / Dev. Biol 325:444~467
Atamas, S. P. / 1996 / An alternative splice variant of human IL-4, IL-4 delta 2, inhibits IL-4-stimulated T cell proliferation / J. Immunol 156:435~441
Baek, S. J. / 2016 / Integrated epigenomic analyses of enhancer as well as promoter regions in gastric cancer / Oncotarget 7:25620~25631
Bernstein, B. E. / 2007 / The mammalian epigenome / Cell 128:669~681
David-Fung, E. S. / 2009 / Transcription factor expression dynamics of early T-lymphocyte specification and commitment / Dev. Biol 325:444~467
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