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ETV2/ER71 regulates the generation of FLK1(+) cells from mouse embryonic stem cells through miR-126-MAPK signaling

Previous studies including ours have demonstrated a critical function of the transcription factor ETV2 (ets variant 2; also known as ER71) in determining the fate of cardiovascular lineage development. However, the underlying mechanisms of ETV2 function remain largely unknown. In this study, we demo...

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Autores principales: Kim, Ju Young, Lee, Dong Hun, Kim, Joo Kyung, Choi, Hong Seo, Dwivedi, Bhakti, Rupji, Manali, Kowalski, Jeanne, Green, Stefan J., Song, Heesang, Park, Won Jong, Chang, Ji Young, Kim, Tae Min, Park, Changwon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862833/
https://www.ncbi.nlm.nih.gov/pubmed/31744543
http://dx.doi.org/10.1186/s13287-019-1466-8
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author Kim, Ju Young
Lee, Dong Hun
Kim, Joo Kyung
Choi, Hong Seo
Dwivedi, Bhakti
Rupji, Manali
Kowalski, Jeanne
Green, Stefan J.
Song, Heesang
Park, Won Jong
Chang, Ji Young
Kim, Tae Min
Park, Changwon
author_facet Kim, Ju Young
Lee, Dong Hun
Kim, Joo Kyung
Choi, Hong Seo
Dwivedi, Bhakti
Rupji, Manali
Kowalski, Jeanne
Green, Stefan J.
Song, Heesang
Park, Won Jong
Chang, Ji Young
Kim, Tae Min
Park, Changwon
author_sort Kim, Ju Young
collection PubMed
description Previous studies including ours have demonstrated a critical function of the transcription factor ETV2 (ets variant 2; also known as ER71) in determining the fate of cardiovascular lineage development. However, the underlying mechanisms of ETV2 function remain largely unknown. In this study, we demonstrated the novel function of the miR (micro RNA)-126-MAPK (mitogen-activated protein kinase) pathway in ETV2-mediated FLK1 (fetal liver kinase 1; also known as VEGFR2)(+) cell generation from the mouse embryonic stem cells (mESCs). By performing a series of experiments including miRNA sequencing and ChIP (chromatin immunoprecipitation)-PCR, we found that miR-126 is directly induced by ETV2. Further, we identified that miR-126 can positively regulate the generation of FLK1(+) cells by activating the MAPK pathway through targeting SPRED1 (sprouty-related EVH1 domain containing 1). Further, we showed evidence that JUN/FOS activate the enhancer region of FLK1 through AP1 (activator protein 1) binding sequences. Our findings provide insight into the novel molecular mechanisms of ETV2 function in regulating cardiovascular lineage development from mESCs.
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spelling pubmed-68628332019-12-11 ETV2/ER71 regulates the generation of FLK1(+) cells from mouse embryonic stem cells through miR-126-MAPK signaling Kim, Ju Young Lee, Dong Hun Kim, Joo Kyung Choi, Hong Seo Dwivedi, Bhakti Rupji, Manali Kowalski, Jeanne Green, Stefan J. Song, Heesang Park, Won Jong Chang, Ji Young Kim, Tae Min Park, Changwon Stem Cell Res Ther Short Report Previous studies including ours have demonstrated a critical function of the transcription factor ETV2 (ets variant 2; also known as ER71) in determining the fate of cardiovascular lineage development. However, the underlying mechanisms of ETV2 function remain largely unknown. In this study, we demonstrated the novel function of the miR (micro RNA)-126-MAPK (mitogen-activated protein kinase) pathway in ETV2-mediated FLK1 (fetal liver kinase 1; also known as VEGFR2)(+) cell generation from the mouse embryonic stem cells (mESCs). By performing a series of experiments including miRNA sequencing and ChIP (chromatin immunoprecipitation)-PCR, we found that miR-126 is directly induced by ETV2. Further, we identified that miR-126 can positively regulate the generation of FLK1(+) cells by activating the MAPK pathway through targeting SPRED1 (sprouty-related EVH1 domain containing 1). Further, we showed evidence that JUN/FOS activate the enhancer region of FLK1 through AP1 (activator protein 1) binding sequences. Our findings provide insight into the novel molecular mechanisms of ETV2 function in regulating cardiovascular lineage development from mESCs. BioMed Central 2019-11-19 /pmc/articles/PMC6862833/ /pubmed/31744543 http://dx.doi.org/10.1186/s13287-019-1466-8 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Short Report
Kim, Ju Young
Lee, Dong Hun
Kim, Joo Kyung
Choi, Hong Seo
Dwivedi, Bhakti
Rupji, Manali
Kowalski, Jeanne
Green, Stefan J.
Song, Heesang
Park, Won Jong
Chang, Ji Young
Kim, Tae Min
Park, Changwon
ETV2/ER71 regulates the generation of FLK1(+) cells from mouse embryonic stem cells through miR-126-MAPK signaling
title ETV2/ER71 regulates the generation of FLK1(+) cells from mouse embryonic stem cells through miR-126-MAPK signaling
title_full ETV2/ER71 regulates the generation of FLK1(+) cells from mouse embryonic stem cells through miR-126-MAPK signaling
title_fullStr ETV2/ER71 regulates the generation of FLK1(+) cells from mouse embryonic stem cells through miR-126-MAPK signaling
title_full_unstemmed ETV2/ER71 regulates the generation of FLK1(+) cells from mouse embryonic stem cells through miR-126-MAPK signaling
title_short ETV2/ER71 regulates the generation of FLK1(+) cells from mouse embryonic stem cells through miR-126-MAPK signaling
title_sort etv2/er71 regulates the generation of flk1(+) cells from mouse embryonic stem cells through mir-126-mapk signaling
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862833/
https://www.ncbi.nlm.nih.gov/pubmed/31744543
http://dx.doi.org/10.1186/s13287-019-1466-8
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