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Inhibition of MicroRNA-221 and 222 Enhances Hematopoietic Differentiation from Human Pluripotent Stem Cells via c-KIT Upregulation

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 hematopoiet...

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Autores principales: Lee, Ji Yoon, Kim, MyungJoo, Heo, Hye-Ryeon, Ha, Kwon-Soo, Han, Eun-Taek, Park, Won Sun, Yang, Se-Ran, Hong, Seok-Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Molecular and Cellular Biology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277561/
https://www.ncbi.nlm.nih.gov/pubmed/30396237
http://dx.doi.org/10.14348/molcells.2018.0244
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author Lee, Ji Yoon
Kim, MyungJoo
Heo, Hye-Ryeon
Ha, Kwon-Soo
Han, Eun-Taek
Park, Won Sun
Yang, Se-Ran
Hong, Seok-Ho
author_facet Lee, Ji Yoon
Kim, MyungJoo
Heo, Hye-Ryeon
Ha, Kwon-Soo
Han, Eun-Taek
Park, Won Sun
Yang, Se-Ran
Hong, Seok-Ho
author_sort Lee, Ji Yoon
collection PubMed
description 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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spelling pubmed-62775612018-12-13 Inhibition of MicroRNA-221 and 222 Enhances Hematopoietic Differentiation from Human Pluripotent Stem Cells via c-KIT Upregulation Lee, Ji Yoon Kim, MyungJoo Heo, Hye-Ryeon Ha, Kwon-Soo Han, Eun-Taek Park, Won Sun Yang, Se-Ran Hong, Seok-Ho Mol Cells Article 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. Korean Society for Molecular and Cellular Biology 2018-11-30 2018-11-01 /pmc/articles/PMC6277561/ /pubmed/30396237 http://dx.doi.org/10.14348/molcells.2018.0244 Text en © The 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/
spellingShingle Article
Lee, Ji Yoon
Kim, MyungJoo
Heo, Hye-Ryeon
Ha, Kwon-Soo
Han, Eun-Taek
Park, Won Sun
Yang, Se-Ran
Hong, Seok-Ho
Inhibition of MicroRNA-221 and 222 Enhances Hematopoietic Differentiation from Human Pluripotent Stem Cells via c-KIT Upregulation
title Inhibition of MicroRNA-221 and 222 Enhances Hematopoietic Differentiation from Human Pluripotent Stem Cells via c-KIT Upregulation
title_full Inhibition of MicroRNA-221 and 222 Enhances Hematopoietic Differentiation from Human Pluripotent Stem Cells via c-KIT Upregulation
title_fullStr Inhibition of MicroRNA-221 and 222 Enhances Hematopoietic Differentiation from Human Pluripotent Stem Cells via c-KIT Upregulation
title_full_unstemmed Inhibition of MicroRNA-221 and 222 Enhances Hematopoietic Differentiation from Human Pluripotent Stem Cells via c-KIT Upregulation
title_short Inhibition of MicroRNA-221 and 222 Enhances Hematopoietic Differentiation from Human Pluripotent Stem Cells via c-KIT Upregulation
title_sort inhibition of microrna-221 and 222 enhances hematopoietic differentiation from human pluripotent stem cells via c-kit upregulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277561/
https://www.ncbi.nlm.nih.gov/pubmed/30396237
http://dx.doi.org/10.14348/molcells.2018.0244
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