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CXCL14 Maintains hESC Self-Renewal through Binding to IGF-1R and Activation of the IGF-1R Pathway

Human embryonic stem cells (hESCs) have important roles in regenerative medicine, but only a few studies have investigated the cytokines secreted by hESCs. We screened and identified chemokine (C-X-C motif) ligand 14 (CXCL14), which plays crucial roles in hESC renewal. CXCL14, a C-X-C motif chemokin...

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Autores principales: Cheng, Chih-Lun, Yang, Shang-Chih, Lai, Chien-Ying, Wang, Cheng-Kai, Chang, Ching-Fang, Lin, Chun-Yu, Chen, Wei-Ju, Lin, Po-Yu, Wu, Han-Chung, Ma, Nianhan, Lu, Frank Leigh, Lu, Jean
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407311/
https://www.ncbi.nlm.nih.gov/pubmed/32708730
http://dx.doi.org/10.3390/cells9071706
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author Cheng, Chih-Lun
Yang, Shang-Chih
Lai, Chien-Ying
Wang, Cheng-Kai
Chang, Ching-Fang
Lin, Chun-Yu
Chen, Wei-Ju
Lin, Po-Yu
Wu, Han-Chung
Ma, Nianhan
Lu, Frank Leigh
Lu, Jean
author_facet Cheng, Chih-Lun
Yang, Shang-Chih
Lai, Chien-Ying
Wang, Cheng-Kai
Chang, Ching-Fang
Lin, Chun-Yu
Chen, Wei-Ju
Lin, Po-Yu
Wu, Han-Chung
Ma, Nianhan
Lu, Frank Leigh
Lu, Jean
author_sort Cheng, Chih-Lun
collection PubMed
description Human embryonic stem cells (hESCs) have important roles in regenerative medicine, but only a few studies have investigated the cytokines secreted by hESCs. We screened and identified chemokine (C-X-C motif) ligand 14 (CXCL14), which plays crucial roles in hESC renewal. CXCL14, a C-X-C motif chemokine, is also named as breast and kidney-expressed chemokine (BRAK), B cell and monocyte-activated chemokine (BMAC), and macrophage inflammatory protein-2γ (MIP-2γ). Knockdown of CXCL14 disrupted the hESC self-renewal, changed cell cycle distribution, and further increased the expression levels of mesoderm and endoderm differentiated markers. Interestingly, we demonstrated that CXCL14 is the ligand for the insulin-like growth factor 1 receptor (IGF-1R), and it can activate IGF-1R signal transduction to support hESC renewal. Currently published literature indicates that all receptors in the CXCL family are G protein-coupled receptors (GPCRs). This report is the first to demonstrate that a CXCL protein can bind to and activate a receptor tyrosine kinase (RTK), and also the first to show that IGF-1R has another ligand in addition to IGFs. These findings broaden our understanding of stem cell biology and signal transduction.
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spelling pubmed-74073112020-08-11 CXCL14 Maintains hESC Self-Renewal through Binding to IGF-1R and Activation of the IGF-1R Pathway Cheng, Chih-Lun Yang, Shang-Chih Lai, Chien-Ying Wang, Cheng-Kai Chang, Ching-Fang Lin, Chun-Yu Chen, Wei-Ju Lin, Po-Yu Wu, Han-Chung Ma, Nianhan Lu, Frank Leigh Lu, Jean Cells Article Human embryonic stem cells (hESCs) have important roles in regenerative medicine, but only a few studies have investigated the cytokines secreted by hESCs. We screened and identified chemokine (C-X-C motif) ligand 14 (CXCL14), which plays crucial roles in hESC renewal. CXCL14, a C-X-C motif chemokine, is also named as breast and kidney-expressed chemokine (BRAK), B cell and monocyte-activated chemokine (BMAC), and macrophage inflammatory protein-2γ (MIP-2γ). Knockdown of CXCL14 disrupted the hESC self-renewal, changed cell cycle distribution, and further increased the expression levels of mesoderm and endoderm differentiated markers. Interestingly, we demonstrated that CXCL14 is the ligand for the insulin-like growth factor 1 receptor (IGF-1R), and it can activate IGF-1R signal transduction to support hESC renewal. Currently published literature indicates that all receptors in the CXCL family are G protein-coupled receptors (GPCRs). This report is the first to demonstrate that a CXCL protein can bind to and activate a receptor tyrosine kinase (RTK), and also the first to show that IGF-1R has another ligand in addition to IGFs. These findings broaden our understanding of stem cell biology and signal transduction. MDPI 2020-07-16 /pmc/articles/PMC7407311/ /pubmed/32708730 http://dx.doi.org/10.3390/cells9071706 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cheng, Chih-Lun
Yang, Shang-Chih
Lai, Chien-Ying
Wang, Cheng-Kai
Chang, Ching-Fang
Lin, Chun-Yu
Chen, Wei-Ju
Lin, Po-Yu
Wu, Han-Chung
Ma, Nianhan
Lu, Frank Leigh
Lu, Jean
CXCL14 Maintains hESC Self-Renewal through Binding to IGF-1R and Activation of the IGF-1R Pathway
title CXCL14 Maintains hESC Self-Renewal through Binding to IGF-1R and Activation of the IGF-1R Pathway
title_full CXCL14 Maintains hESC Self-Renewal through Binding to IGF-1R and Activation of the IGF-1R Pathway
title_fullStr CXCL14 Maintains hESC Self-Renewal through Binding to IGF-1R and Activation of the IGF-1R Pathway
title_full_unstemmed CXCL14 Maintains hESC Self-Renewal through Binding to IGF-1R and Activation of the IGF-1R Pathway
title_short CXCL14 Maintains hESC Self-Renewal through Binding to IGF-1R and Activation of the IGF-1R Pathway
title_sort cxcl14 maintains hesc self-renewal through binding to igf-1r and activation of the igf-1r pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407311/
https://www.ncbi.nlm.nih.gov/pubmed/32708730
http://dx.doi.org/10.3390/cells9071706
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