Cargando…

Alpha lipoic acid promotes development of hematopoietic progenitors derived from human embryonic stem cells by antagonizing ROS signals

Antagonism of ROS signaling can inhibit cell apoptosis and autophagy, thus favoring the maintenance and expansion of hematopoietic stem cells. Alpha lipoic acid (ALA), a small antioxidant molecule, affects cell apoptosis by lowering the ROS level. In this study, we show that ALA promoted production...

Descripción completa

Detalles Bibliográficos
Autores principales: Dong, Yong, Bai, Ju, Zhang, Yimeng, Zhou, Ya, Pan, Xu, Li, Xiaohong, Zhou, Qiongxiu, Chen, Yijin, Lai, Mowen, Mao, Bin, Bian, Guohui, Feng, Jia, Xie, Fangxin, Chen, Bo, Nakahata, Tatsutoshi, Zhang, Yonggang, Ma, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754144/
https://www.ncbi.nlm.nih.gov/pubmed/32640500
http://dx.doi.org/10.1002/JLB.1A0520-179R
_version_ 1783626135174643712
author Dong, Yong
Bai, Ju
Zhang, Yimeng
Zhou, Ya
Pan, Xu
Li, Xiaohong
Zhou, Qiongxiu
Chen, Yijin
Lai, Mowen
Mao, Bin
Bian, Guohui
Feng, Jia
Xie, Fangxin
Chen, Bo
Nakahata, Tatsutoshi
Zhang, Yonggang
Ma, Feng
author_facet Dong, Yong
Bai, Ju
Zhang, Yimeng
Zhou, Ya
Pan, Xu
Li, Xiaohong
Zhou, Qiongxiu
Chen, Yijin
Lai, Mowen
Mao, Bin
Bian, Guohui
Feng, Jia
Xie, Fangxin
Chen, Bo
Nakahata, Tatsutoshi
Zhang, Yonggang
Ma, Feng
author_sort Dong, Yong
collection PubMed
description Antagonism of ROS signaling can inhibit cell apoptosis and autophagy, thus favoring the maintenance and expansion of hematopoietic stem cells. Alpha lipoic acid (ALA), a small antioxidant molecule, affects cell apoptosis by lowering the ROS level. In this study, we show that ALA promoted production of human pluripotent stem cells (hPSCs) derived hemogenic endothelial cells and hematopoietic stem/progenitor cells in vitro. Transcriptome analysis of hPSCs derived hemogenic endothelial cells showed that ALA promoted endothelial‐to‐hematopoietic transition by up‐regulating RUNX1, GFI1, GFI1B, MEIS2, and HIF1A and down‐regulating SOX17, TGFB1, TGFB2, TGFB3, TGFBR1, and TGFBR2. ALA also up‐regulated sensor genes of ROS signals, including HIF1A, FOXO1, FOXO3, ATM, PETEN, SIRT1, and SIRT3, during the process of hPSCs derived hemogenic endothelial cells generation. However, in more mature hPSC‐derived hematopoietic stem/progenitor cells, ALA reduced ROS levels and inhibited apoptosis. In particular, ALA enhanced development of hPSCs derived hematopoietic stem/progenitor cells by up‐regulating HIF1A in response to a hypoxic environment. Furthermore, addition of ALA in ex vivo culture greatly improved the maintenance of functional cord blood HSCs by in vivo transplantation assay. Our findings support the conjecture that ALA plays an important role in efficient regeneration of hematopoietic stem/progenitor cells from hPSCs and maintenance of functional HSCs, providing insight into understanding of regeneration of early hematopoiesis for engineering clinically useful hPSCs derived hematopoietic stem/progenitor cells transplantation. Thus, ALA can be used in the study of hPSCs derived HSCs.
format Online
Article
Text
id pubmed-7754144
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-77541442020-12-23 Alpha lipoic acid promotes development of hematopoietic progenitors derived from human embryonic stem cells by antagonizing ROS signals Dong, Yong Bai, Ju Zhang, Yimeng Zhou, Ya Pan, Xu Li, Xiaohong Zhou, Qiongxiu Chen, Yijin Lai, Mowen Mao, Bin Bian, Guohui Feng, Jia Xie, Fangxin Chen, Bo Nakahata, Tatsutoshi Zhang, Yonggang Ma, Feng J Leukoc Biol Cell Development, Differentiation, & Trafficking Antagonism of ROS signaling can inhibit cell apoptosis and autophagy, thus favoring the maintenance and expansion of hematopoietic stem cells. Alpha lipoic acid (ALA), a small antioxidant molecule, affects cell apoptosis by lowering the ROS level. In this study, we show that ALA promoted production of human pluripotent stem cells (hPSCs) derived hemogenic endothelial cells and hematopoietic stem/progenitor cells in vitro. Transcriptome analysis of hPSCs derived hemogenic endothelial cells showed that ALA promoted endothelial‐to‐hematopoietic transition by up‐regulating RUNX1, GFI1, GFI1B, MEIS2, and HIF1A and down‐regulating SOX17, TGFB1, TGFB2, TGFB3, TGFBR1, and TGFBR2. ALA also up‐regulated sensor genes of ROS signals, including HIF1A, FOXO1, FOXO3, ATM, PETEN, SIRT1, and SIRT3, during the process of hPSCs derived hemogenic endothelial cells generation. However, in more mature hPSC‐derived hematopoietic stem/progenitor cells, ALA reduced ROS levels and inhibited apoptosis. In particular, ALA enhanced development of hPSCs derived hematopoietic stem/progenitor cells by up‐regulating HIF1A in response to a hypoxic environment. Furthermore, addition of ALA in ex vivo culture greatly improved the maintenance of functional cord blood HSCs by in vivo transplantation assay. Our findings support the conjecture that ALA plays an important role in efficient regeneration of hematopoietic stem/progenitor cells from hPSCs and maintenance of functional HSCs, providing insight into understanding of regeneration of early hematopoiesis for engineering clinically useful hPSCs derived hematopoietic stem/progenitor cells transplantation. Thus, ALA can be used in the study of hPSCs derived HSCs. John Wiley and Sons Inc. 2020-07-08 2020-12 /pmc/articles/PMC7754144/ /pubmed/32640500 http://dx.doi.org/10.1002/JLB.1A0520-179R Text en © 2020 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals LLC on behalf of Society for Leukocyte Biology This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Cell Development, Differentiation, & Trafficking
Dong, Yong
Bai, Ju
Zhang, Yimeng
Zhou, Ya
Pan, Xu
Li, Xiaohong
Zhou, Qiongxiu
Chen, Yijin
Lai, Mowen
Mao, Bin
Bian, Guohui
Feng, Jia
Xie, Fangxin
Chen, Bo
Nakahata, Tatsutoshi
Zhang, Yonggang
Ma, Feng
Alpha lipoic acid promotes development of hematopoietic progenitors derived from human embryonic stem cells by antagonizing ROS signals
title Alpha lipoic acid promotes development of hematopoietic progenitors derived from human embryonic stem cells by antagonizing ROS signals
title_full Alpha lipoic acid promotes development of hematopoietic progenitors derived from human embryonic stem cells by antagonizing ROS signals
title_fullStr Alpha lipoic acid promotes development of hematopoietic progenitors derived from human embryonic stem cells by antagonizing ROS signals
title_full_unstemmed Alpha lipoic acid promotes development of hematopoietic progenitors derived from human embryonic stem cells by antagonizing ROS signals
title_short Alpha lipoic acid promotes development of hematopoietic progenitors derived from human embryonic stem cells by antagonizing ROS signals
title_sort alpha lipoic acid promotes development of hematopoietic progenitors derived from human embryonic stem cells by antagonizing ros signals
topic Cell Development, Differentiation, & Trafficking
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754144/
https://www.ncbi.nlm.nih.gov/pubmed/32640500
http://dx.doi.org/10.1002/JLB.1A0520-179R
work_keys_str_mv AT dongyong alphalipoicacidpromotesdevelopmentofhematopoieticprogenitorsderivedfromhumanembryonicstemcellsbyantagonizingrossignals
AT baiju alphalipoicacidpromotesdevelopmentofhematopoieticprogenitorsderivedfromhumanembryonicstemcellsbyantagonizingrossignals
AT zhangyimeng alphalipoicacidpromotesdevelopmentofhematopoieticprogenitorsderivedfromhumanembryonicstemcellsbyantagonizingrossignals
AT zhouya alphalipoicacidpromotesdevelopmentofhematopoieticprogenitorsderivedfromhumanembryonicstemcellsbyantagonizingrossignals
AT panxu alphalipoicacidpromotesdevelopmentofhematopoieticprogenitorsderivedfromhumanembryonicstemcellsbyantagonizingrossignals
AT lixiaohong alphalipoicacidpromotesdevelopmentofhematopoieticprogenitorsderivedfromhumanembryonicstemcellsbyantagonizingrossignals
AT zhouqiongxiu alphalipoicacidpromotesdevelopmentofhematopoieticprogenitorsderivedfromhumanembryonicstemcellsbyantagonizingrossignals
AT chenyijin alphalipoicacidpromotesdevelopmentofhematopoieticprogenitorsderivedfromhumanembryonicstemcellsbyantagonizingrossignals
AT laimowen alphalipoicacidpromotesdevelopmentofhematopoieticprogenitorsderivedfromhumanembryonicstemcellsbyantagonizingrossignals
AT maobin alphalipoicacidpromotesdevelopmentofhematopoieticprogenitorsderivedfromhumanembryonicstemcellsbyantagonizingrossignals
AT bianguohui alphalipoicacidpromotesdevelopmentofhematopoieticprogenitorsderivedfromhumanembryonicstemcellsbyantagonizingrossignals
AT fengjia alphalipoicacidpromotesdevelopmentofhematopoieticprogenitorsderivedfromhumanembryonicstemcellsbyantagonizingrossignals
AT xiefangxin alphalipoicacidpromotesdevelopmentofhematopoieticprogenitorsderivedfromhumanembryonicstemcellsbyantagonizingrossignals
AT chenbo alphalipoicacidpromotesdevelopmentofhematopoieticprogenitorsderivedfromhumanembryonicstemcellsbyantagonizingrossignals
AT nakahatatatsutoshi alphalipoicacidpromotesdevelopmentofhematopoieticprogenitorsderivedfromhumanembryonicstemcellsbyantagonizingrossignals
AT zhangyonggang alphalipoicacidpromotesdevelopmentofhematopoieticprogenitorsderivedfromhumanembryonicstemcellsbyantagonizingrossignals
AT mafeng alphalipoicacidpromotesdevelopmentofhematopoieticprogenitorsderivedfromhumanembryonicstemcellsbyantagonizingrossignals