Mol. Cells 2018; 41(11):   https://doi.org/10.14348/molcells.2018.0213
Dynamic Transcriptome, DNA Methylome, and DNA Hydroxymethylome Networks During T-Cell Lineage Commitment
Byoung-Ha Yoon1,2,4, Mirang Kim1,2,4, Min-Hyeok Kim3, Hee-Jin Kim2, Jeong-Hwan Kim2, Jong Hwan Kim1,2, Jina Kim1,2, Yong Sung Kim1,2, Daeyoup Lee3, Suk-Jo Kang3, and Seon-Young Kim1,2,*
1Department of Functional Genomics, University of Science and Technology (UST), Daejeon, Korea, 2Genome Editing Research Center, Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea, 3Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea
Correspondence: kimsy@kribb.re.kr
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.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit (http://creativecommons.org/licenses/by-nc-sa/3.0/).
ABSTRACT
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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