Mol. Cells 2018; 41(11):
Inhibition of MicroRNA-221 and 222 Enhances Hematopoietic Differentiation from Human Pluripotent Stem Cells via c-KIT Upregulation
Ji Yoon Lee1, MyungJoo Kim2, Hye-Ryeon Heo2, Kwon-Soo Ha3, Eun-Taek Han4, Won Sun Park5, Se-Ran Yang6, and Seok-Ho Hong2,*
1Department of Biomedical Sciences, Stem Cell Institute, CHA University, Seongnam, Korea, 2Department of Internal Medicine,
3Department of Molecular and Cellular Biochemistry, 4Department of Medical Environmental Biology and Tropical Medicine,
5Department of Physiology, 6Department of Thoracic & Cardiovascular Surgery, School of Medicine, Kangwon National University,
Chuncheon 24341, Korea
Received June 2, 2018; Revised August 27, 2018; Accepted October 10, 2018.; Published online November 1, 2018.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

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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.
Keywords: c-KIT, hematopoiesis, hPSCs, miR-221/222, SCF

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31 October 2018 Volume 41,
Number 10, pp. 881~932

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