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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Korean Society for Molecular and Cellular Biology
2018
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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. |
format | Online Article Text |
id | pubmed-6277561 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Korean Society for Molecular and Cellular Biology |
record_format | MEDLINE/PubMed |
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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