Integrative Studies of Human Cord Blood Derived Mononuclear Cells and Umbilical Cord Derived Mesenchyme Stem Cells in Ameliorating Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) is a common pulmonary complication observed in preterm infants that is composed of multifactorial pathogenesis. Current strategies, albeit successful in moderately reducing morbidity and mortality of BPD, failed to draw overall satisfactory conclusion. Here, using a...

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Autores principales:	Jia Chen, Yuhan Chen, Xue Du, Guojun Liu, Xiaowei Fei, Jian Ru Peng, Xing Zhang, Fengjun Xiao, Xue Wang, Xiao Yang, Zhichun Feng
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	bronchopulmonary dysplasia cord blood mononuclear cell umbilical cord mesenchymal stem cells cytokines whole transcriptome sequencing noncoding RNA Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/fd9a746d6a934f359e1850b8817eafe7
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spelling	oai:doaj.org-article:fd9a746d6a934f359e1850b8817eafe72021-11-09T16:38:17ZIntegrative Studies of Human Cord Blood Derived Mononuclear Cells and Umbilical Cord Derived Mesenchyme Stem Cells in Ameliorating Bronchopulmonary Dysplasia2296-634X10.3389/fcell.2021.679866https://doaj.org/article/fd9a746d6a934f359e1850b8817eafe72021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.679866/fullhttps://doaj.org/toc/2296-634XBronchopulmonary dysplasia (BPD) is a common pulmonary complication observed in preterm infants that is composed of multifactorial pathogenesis. Current strategies, albeit successful in moderately reducing morbidity and mortality of BPD, failed to draw overall satisfactory conclusion. Here, using a typical mouse model mimicking hallmarks of BPD, we revealed that both cord blood-derived mononuclear cells (CB-MNCs) and umbilical cord-derived mesenchymal stem cells (UC-MSCs) are efficient in alleviating BPD. Notably, infusion of CB-MNCs has more prominent effects in preventing alveolar simplification and pulmonary vessel loss, restoring pulmonary respiratory functions and balancing inflammatory responses. To further elucidate the underlying mechanisms within the divergent therapeutic effects of UC-MSC and CB-MNC, we systematically investigated the long noncoding RNA (lncRNA)–microRNA (miRNA)–messenger RNA (mRNA) and circular RNA (circRNA)–miRNA–mRNA networks by whole-transcriptome sequencing. Importantly, pathway analysis integrating Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG)/gene set enrichment analysis (GSEA) method indicates that the competing endogenous RNA (ceRNA) network is mainly related to the regulation of GTPase activity (GO: 0043087), extracellular signal-regulated kinase 1 (ERK1) and ERK2 signal cascade (GO: 0070371), chromosome regulation (GO: 0007059), and cell cycle control (GO: 0044770). Through rigorous selection of the lncRNA/circRNA-based ceRNA network, we demonstrated that the hub genes reside in UC-MSC- and CB-MNC-infused networks directed to the function of cell adhesion, motor transportation (Cdk13, Lrrn2), immune homeostasis balance, and autophagy (Homer3, Prkcd) relatively. Our studies illustrate the first comprehensive mRNA–miRNA–lncRNA and mRNA–miRNA–circRNA networks in stem cell-infused BPD model, which will be valuable in identifying reliable biomarkers or therapeutic targets for BPD pathogenesis and shed new light in the priming and conditioning of UC-MSCs or CB-MNCs in the treatment of neonatal lung injury.Jia ChenJia ChenJia ChenJia ChenYuhan ChenYuhan ChenYuhan ChenXue DuXue DuXue DuXue DuGuojun LiuXiaowei FeiXiaowei FeiJian Ru PengJian Ru PengJian Ru PengJian Ru PengXing ZhangXing ZhangXing ZhangFengjun XiaoXue WangXiao YangXiao YangXiao YangZhichun FengZhichun FengZhichun FengZhichun FengZhichun FengFrontiers Media S.A.articlebronchopulmonary dysplasiacord blood mononuclear cellumbilical cord mesenchymal stem cellscytokineswhole transcriptome sequencingnoncoding RNABiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bronchopulmonary dysplasia cord blood mononuclear cell umbilical cord mesenchymal stem cells cytokines whole transcriptome sequencing noncoding RNA Biology (General) QH301-705.5
spellingShingle	bronchopulmonary dysplasia cord blood mononuclear cell umbilical cord mesenchymal stem cells cytokines whole transcriptome sequencing noncoding RNA Biology (General) QH301-705.5 Jia Chen Jia Chen Jia Chen Jia Chen Yuhan Chen Yuhan Chen Yuhan Chen Xue Du Xue Du Xue Du Xue Du Guojun Liu Xiaowei Fei Xiaowei Fei Jian Ru Peng Jian Ru Peng Jian Ru Peng Jian Ru Peng Xing Zhang Xing Zhang Xing Zhang Fengjun Xiao Xue Wang Xiao Yang Xiao Yang Xiao Yang Zhichun Feng Zhichun Feng Zhichun Feng Zhichun Feng Zhichun Feng Integrative Studies of Human Cord Blood Derived Mononuclear Cells and Umbilical Cord Derived Mesenchyme Stem Cells in Ameliorating Bronchopulmonary Dysplasia
description	Bronchopulmonary dysplasia (BPD) is a common pulmonary complication observed in preterm infants that is composed of multifactorial pathogenesis. Current strategies, albeit successful in moderately reducing morbidity and mortality of BPD, failed to draw overall satisfactory conclusion. Here, using a typical mouse model mimicking hallmarks of BPD, we revealed that both cord blood-derived mononuclear cells (CB-MNCs) and umbilical cord-derived mesenchymal stem cells (UC-MSCs) are efficient in alleviating BPD. Notably, infusion of CB-MNCs has more prominent effects in preventing alveolar simplification and pulmonary vessel loss, restoring pulmonary respiratory functions and balancing inflammatory responses. To further elucidate the underlying mechanisms within the divergent therapeutic effects of UC-MSC and CB-MNC, we systematically investigated the long noncoding RNA (lncRNA)–microRNA (miRNA)–messenger RNA (mRNA) and circular RNA (circRNA)–miRNA–mRNA networks by whole-transcriptome sequencing. Importantly, pathway analysis integrating Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG)/gene set enrichment analysis (GSEA) method indicates that the competing endogenous RNA (ceRNA) network is mainly related to the regulation of GTPase activity (GO: 0043087), extracellular signal-regulated kinase 1 (ERK1) and ERK2 signal cascade (GO: 0070371), chromosome regulation (GO: 0007059), and cell cycle control (GO: 0044770). Through rigorous selection of the lncRNA/circRNA-based ceRNA network, we demonstrated that the hub genes reside in UC-MSC- and CB-MNC-infused networks directed to the function of cell adhesion, motor transportation (Cdk13, Lrrn2), immune homeostasis balance, and autophagy (Homer3, Prkcd) relatively. Our studies illustrate the first comprehensive mRNA–miRNA–lncRNA and mRNA–miRNA–circRNA networks in stem cell-infused BPD model, which will be valuable in identifying reliable biomarkers or therapeutic targets for BPD pathogenesis and shed new light in the priming and conditioning of UC-MSCs or CB-MNCs in the treatment of neonatal lung injury.
format	article
author	Jia Chen Jia Chen Jia Chen Jia Chen Yuhan Chen Yuhan Chen Yuhan Chen Xue Du Xue Du Xue Du Xue Du Guojun Liu Xiaowei Fei Xiaowei Fei Jian Ru Peng Jian Ru Peng Jian Ru Peng Jian Ru Peng Xing Zhang Xing Zhang Xing Zhang Fengjun Xiao Xue Wang Xiao Yang Xiao Yang Xiao Yang Zhichun Feng Zhichun Feng Zhichun Feng Zhichun Feng Zhichun Feng
author_facet	Jia Chen Jia Chen Jia Chen Jia Chen Yuhan Chen Yuhan Chen Yuhan Chen Xue Du Xue Du Xue Du Xue Du Guojun Liu Xiaowei Fei Xiaowei Fei Jian Ru Peng Jian Ru Peng Jian Ru Peng Jian Ru Peng Xing Zhang Xing Zhang Xing Zhang Fengjun Xiao Xue Wang Xiao Yang Xiao Yang Xiao Yang Zhichun Feng Zhichun Feng Zhichun Feng Zhichun Feng Zhichun Feng
author_sort	Jia Chen
title	Integrative Studies of Human Cord Blood Derived Mononuclear Cells and Umbilical Cord Derived Mesenchyme Stem Cells in Ameliorating Bronchopulmonary Dysplasia
title_short	Integrative Studies of Human Cord Blood Derived Mononuclear Cells and Umbilical Cord Derived Mesenchyme Stem Cells in Ameliorating Bronchopulmonary Dysplasia
title_full	Integrative Studies of Human Cord Blood Derived Mononuclear Cells and Umbilical Cord Derived Mesenchyme Stem Cells in Ameliorating Bronchopulmonary Dysplasia
title_fullStr	Integrative Studies of Human Cord Blood Derived Mononuclear Cells and Umbilical Cord Derived Mesenchyme Stem Cells in Ameliorating Bronchopulmonary Dysplasia
title_full_unstemmed	Integrative Studies of Human Cord Blood Derived Mononuclear Cells and Umbilical Cord Derived Mesenchyme Stem Cells in Ameliorating Bronchopulmonary Dysplasia
title_sort	integrative studies of human cord blood derived mononuclear cells and umbilical cord derived mesenchyme stem cells in ameliorating bronchopulmonary dysplasia
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/fd9a746d6a934f359e1850b8817eafe7
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Integrative Studies of Human Cord Blood Derived Mononuclear Cells and Umbilical Cord Derived Mesenchyme Stem Cells in Ameliorating Bronchopulmonary Dysplasia

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