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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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.679866/full |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T02:33:30Z |
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| language | English |
| last_indexed | 2024-12-21T02:33:30Z |
| publishDate | 2021-11-01 |
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| spelling | doaj.art-fd9a746d6a934f359e1850b8817eafe72022-12-21T19:18:51ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-11-01910.3389/fcell.2021.679866679866Integrative Studies of Human Cord Blood Derived Mononuclear Cells and Umbilical Cord Derived Mesenchyme Stem Cells in Ameliorating Bronchopulmonary DysplasiaJia Chen0Jia Chen1Jia Chen2Jia Chen3Yuhan Chen4Yuhan Chen5Yuhan Chen6Xue Du7Xue Du8Xue Du9Xue Du10Guojun Liu11Xiaowei Fei12Xiaowei Fei13Jian Ru Peng14Jian Ru Peng15Jian Ru Peng16Jian Ru Peng17Xing Zhang18Xing Zhang19Xing Zhang20Fengjun Xiao21Xue Wang22Xiao Yang23Xiao Yang24Xiao Yang25Zhichun Feng26Zhichun Feng27Zhichun Feng28Zhichun Feng29Zhichun Feng30The Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Neonatology, Senior Department of Pediatrics, The Seventh Medical Center of PLA General Hospital, Beijing, ChinaNational Engineering Laboratory for Birth Defects Prevention and Control of Key Technology, Beijing, ChinaBeijing Key Laboratory of Pediatric Organ Failure, Beijing, ChinaDepartment of Neonatology, Senior Department of Pediatrics, The Seventh Medical Center of PLA General Hospital, Beijing, ChinaNational Engineering Laboratory for Birth Defects Prevention and Control of Key Technology, Beijing, ChinaBeijing Key Laboratory of Pediatric Organ Failure, Beijing, ChinaDepartment of Neonatology, Senior Department of Pediatrics, The Seventh Medical Center of PLA General Hospital, Beijing, ChinaNational Engineering Laboratory for Birth Defects Prevention and Control of Key Technology, Beijing, ChinaBeijing Key Laboratory of Pediatric Organ Failure, Beijing, ChinaThe First Affiliated Hospital of Dalian Medical University, Dalian, ChinaShandong Qilu Stem Cell Engineering Co., Ltd., Jinan, ChinaThe First Affiliated Hospital of Dalian Medical University, Dalian, ChinaDepartment of Neurosurgery, Xijing Hospital, Air Force Military Medical University, Xi’an, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Neonatology, Senior Department of Pediatrics, The Seventh Medical Center of PLA General Hospital, Beijing, ChinaNational Engineering Laboratory for Birth Defects Prevention and Control of Key Technology, Beijing, ChinaBeijing Key Laboratory of Pediatric Organ Failure, Beijing, ChinaDepartment of Neonatology, Senior Department of Pediatrics, The Seventh Medical Center of PLA General Hospital, Beijing, ChinaNational Engineering Laboratory for Birth Defects Prevention and Control of Key Technology, Beijing, ChinaBeijing Key Laboratory of Pediatric Organ Failure, Beijing, ChinaDepartment of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, ChinaExperimental Research Center, China Academy of Chinese Medical Sciences, Beijing, ChinaDepartment of Neonatology, Senior Department of Pediatrics, The Seventh Medical Center of PLA General Hospital, Beijing, ChinaNational Engineering Laboratory for Birth Defects Prevention and Control of Key Technology, Beijing, ChinaBeijing Key Laboratory of Pediatric Organ Failure, Beijing, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Neonatology, Senior Department of Pediatrics, The Seventh Medical Center of PLA General Hospital, Beijing, ChinaNational Engineering Laboratory for Birth Defects Prevention and Control of Key Technology, Beijing, ChinaBeijing Key Laboratory of Pediatric Organ Failure, Beijing, ChinaThe First Affiliated Hospital of Dalian Medical University, Dalian, ChinaBronchopulmonary 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.679866/fullbronchopulmonary dysplasiacord blood mononuclear cellumbilical cord mesenchymal stem cellscytokineswhole transcriptome sequencingnoncoding RNA |
| spellingShingle | 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 Frontiers in Cell and Developmental Biology bronchopulmonary dysplasia cord blood mononuclear cell umbilical cord mesenchymal stem cells cytokines whole transcriptome sequencing noncoding RNA |
| title | 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_short | 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 |
| topic | bronchopulmonary dysplasia cord blood mononuclear cell umbilical cord mesenchymal stem cells cytokines whole transcriptome sequencing noncoding RNA |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.679866/full |
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