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Targeting JNK pathway promotes human hematopoietic stem cell expansion

The limited number of human hematopoietic stem cells (HSCs) has restrained their widespread clinical application. Despite great efforts in recent years, the in vitro expansion of HSCs remains a challenge due to incomplete understanding of the signaling networks underlying HSC self-renewal. Here, we...

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Autores principales: Xiao, Xiong, Lai, Weifeng, Xie, Huangfan, Liu, Yang, Guo, Weijie, Liu, Yifang, Li, Yu, Li, Yuanjun, Zhang, Jingliang, Chen, Wenhan, Shi, Minhui, Shang, Lijun, Yin, Ming, Wang, Chengyan, Deng, Hongkui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323118/
https://www.ncbi.nlm.nih.gov/pubmed/30622738
http://dx.doi.org/10.1038/s41421-018-0072-8
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author Xiao, Xiong
Lai, Weifeng
Xie, Huangfan
Liu, Yang
Guo, Weijie
Liu, Yifang
Li, Yu
Li, Yuanjun
Zhang, Jingliang
Chen, Wenhan
Shi, Minhui
Shang, Lijun
Yin, Ming
Wang, Chengyan
Deng, Hongkui
author_facet Xiao, Xiong
Lai, Weifeng
Xie, Huangfan
Liu, Yang
Guo, Weijie
Liu, Yifang
Li, Yu
Li, Yuanjun
Zhang, Jingliang
Chen, Wenhan
Shi, Minhui
Shang, Lijun
Yin, Ming
Wang, Chengyan
Deng, Hongkui
author_sort Xiao, Xiong
collection PubMed
description The limited number of human hematopoietic stem cells (HSCs) has restrained their widespread clinical application. Despite great efforts in recent years, the in vitro expansion of HSCs remains a challenge due to incomplete understanding of the signaling networks underlying HSC self-renewal. Here, we show that culturing human cord blood (CB) CD34(+) cells with JNK-IN-8, an inhibitor of the JNK signaling pathway, can enhance the self-renewal of HSCs with a 3.88-fold increase in cell number. These cultured CD34(+) cells repopulated recipient mice for 21 weeks and can form secondary engraftment that lasted for more than 21 weeks. Knockdown of c-Jun, a major downstream target in the JNK pathway, promoted the expansion of hematopoietic stem and progenitor cells (HSPCs). Our findings demonstrate a critical role of the JNK pathway in regulating HSC expansion, provide new insights into HSC self-renewal mechanism, and may lead to improved clinical application of HSCs.
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spelling pubmed-63231182019-01-08 Targeting JNK pathway promotes human hematopoietic stem cell expansion Xiao, Xiong Lai, Weifeng Xie, Huangfan Liu, Yang Guo, Weijie Liu, Yifang Li, Yu Li, Yuanjun Zhang, Jingliang Chen, Wenhan Shi, Minhui Shang, Lijun Yin, Ming Wang, Chengyan Deng, Hongkui Cell Discov Article The limited number of human hematopoietic stem cells (HSCs) has restrained their widespread clinical application. Despite great efforts in recent years, the in vitro expansion of HSCs remains a challenge due to incomplete understanding of the signaling networks underlying HSC self-renewal. Here, we show that culturing human cord blood (CB) CD34(+) cells with JNK-IN-8, an inhibitor of the JNK signaling pathway, can enhance the self-renewal of HSCs with a 3.88-fold increase in cell number. These cultured CD34(+) cells repopulated recipient mice for 21 weeks and can form secondary engraftment that lasted for more than 21 weeks. Knockdown of c-Jun, a major downstream target in the JNK pathway, promoted the expansion of hematopoietic stem and progenitor cells (HSPCs). Our findings demonstrate a critical role of the JNK pathway in regulating HSC expansion, provide new insights into HSC self-renewal mechanism, and may lead to improved clinical application of HSCs. Nature Publishing Group UK 2019-01-08 /pmc/articles/PMC6323118/ /pubmed/30622738 http://dx.doi.org/10.1038/s41421-018-0072-8 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Xiao, Xiong
Lai, Weifeng
Xie, Huangfan
Liu, Yang
Guo, Weijie
Liu, Yifang
Li, Yu
Li, Yuanjun
Zhang, Jingliang
Chen, Wenhan
Shi, Minhui
Shang, Lijun
Yin, Ming
Wang, Chengyan
Deng, Hongkui
Targeting JNK pathway promotes human hematopoietic stem cell expansion
title Targeting JNK pathway promotes human hematopoietic stem cell expansion
title_full Targeting JNK pathway promotes human hematopoietic stem cell expansion
title_fullStr Targeting JNK pathway promotes human hematopoietic stem cell expansion
title_full_unstemmed Targeting JNK pathway promotes human hematopoietic stem cell expansion
title_short Targeting JNK pathway promotes human hematopoietic stem cell expansion
title_sort targeting jnk pathway promotes human hematopoietic stem cell expansion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323118/
https://www.ncbi.nlm.nih.gov/pubmed/30622738
http://dx.doi.org/10.1038/s41421-018-0072-8
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