Endothelin-1–Endothelin receptor B complex contributes to oligodendrocyte differentiation and myelin deficits during preterm white matter injury
Preterm cerebral white matter injury (WMI), a major form of prenatal brain injury, may potentially be treated by oligodendrocyte (OL) precursor cell (OPC) transplantation. However, the defective differentiation of OPCs during WMI seriously hampers the clinical application of OPC transplantation. Thu...
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Frontiers Media S.A.
2023-03-01
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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.2023.1163400/full |
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author | Mengjie Du Na Wang Xiaolong Xin Chun-Lan Yan Yan Gu Liang Wang Ying Shen |
author_facet | Mengjie Du Na Wang Xiaolong Xin Chun-Lan Yan Yan Gu Liang Wang Ying Shen |
author_sort | Mengjie Du |
collection | DOAJ |
description | Preterm cerebral white matter injury (WMI), a major form of prenatal brain injury, may potentially be treated by oligodendrocyte (OL) precursor cell (OPC) transplantation. However, the defective differentiation of OPCs during WMI seriously hampers the clinical application of OPC transplantation. Thus, improving the ability of transplanted OPCs to differentiate is critical to OPC transplantation therapy for WMI. We established a hypoxia–ischemia-induced preterm WMI model in mice and screened the molecules affected by WMI using single-cell RNA sequencing. We revealed that endothelin (ET)-1 and endothelin receptor B (ETB) are a pair of signaling molecules responsible for the interaction between neurons and OPCs and that preterm WMI led to an increase in the number of ETB-positive OPCs and premyelinating OLs. Furthermore, the maturation of OLs was reduced by knocking out ETB but promoted by stimulating ET-1/ETB signaling. Our research reveals a new signaling module for neuron–OPC interaction and provides new insight for therapy targeting preterm WMI. |
first_indexed | 2024-04-09T23:54:04Z |
format | Article |
id | doaj.art-daaa1525433f42bb8bcfa3c9045bb827 |
institution | Directory Open Access Journal |
issn | 2296-634X |
language | English |
last_indexed | 2024-04-09T23:54:04Z |
publishDate | 2023-03-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Cell and Developmental Biology |
spelling | doaj.art-daaa1525433f42bb8bcfa3c9045bb8272023-03-17T04:53:19ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-03-011110.3389/fcell.2023.11634001163400Endothelin-1–Endothelin receptor B complex contributes to oligodendrocyte differentiation and myelin deficits during preterm white matter injuryMengjie Du0Na Wang1Xiaolong Xin2Chun-Lan Yan3Yan Gu4Liang Wang5Ying Shen6Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Physiology and Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaNHC and CAMS Key Laboratory of Medical Neurobiology, Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Stem Cell Biology, Zhejiang University School of Medicine, Hangzhou, ChinaNHC and CAMS Key Laboratory of Medical Neurobiology, Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Physiology and Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaPreterm cerebral white matter injury (WMI), a major form of prenatal brain injury, may potentially be treated by oligodendrocyte (OL) precursor cell (OPC) transplantation. However, the defective differentiation of OPCs during WMI seriously hampers the clinical application of OPC transplantation. Thus, improving the ability of transplanted OPCs to differentiate is critical to OPC transplantation therapy for WMI. We established a hypoxia–ischemia-induced preterm WMI model in mice and screened the molecules affected by WMI using single-cell RNA sequencing. We revealed that endothelin (ET)-1 and endothelin receptor B (ETB) are a pair of signaling molecules responsible for the interaction between neurons and OPCs and that preterm WMI led to an increase in the number of ETB-positive OPCs and premyelinating OLs. Furthermore, the maturation of OLs was reduced by knocking out ETB but promoted by stimulating ET-1/ETB signaling. Our research reveals a new signaling module for neuron–OPC interaction and provides new insight for therapy targeting preterm WMI.https://www.frontiersin.org/articles/10.3389/fcell.2023.1163400/fullwhite matter injuryneuron-glia interactionoligodendrocyte precursor cellsingle-cell RNA sequencingmyelination |
spellingShingle | Mengjie Du Na Wang Xiaolong Xin Chun-Lan Yan Yan Gu Liang Wang Ying Shen Endothelin-1–Endothelin receptor B complex contributes to oligodendrocyte differentiation and myelin deficits during preterm white matter injury Frontiers in Cell and Developmental Biology white matter injury neuron-glia interaction oligodendrocyte precursor cell single-cell RNA sequencing myelination |
title | Endothelin-1–Endothelin receptor B complex contributes to oligodendrocyte differentiation and myelin deficits during preterm white matter injury |
title_full | Endothelin-1–Endothelin receptor B complex contributes to oligodendrocyte differentiation and myelin deficits during preterm white matter injury |
title_fullStr | Endothelin-1–Endothelin receptor B complex contributes to oligodendrocyte differentiation and myelin deficits during preterm white matter injury |
title_full_unstemmed | Endothelin-1–Endothelin receptor B complex contributes to oligodendrocyte differentiation and myelin deficits during preterm white matter injury |
title_short | Endothelin-1–Endothelin receptor B complex contributes to oligodendrocyte differentiation and myelin deficits during preterm white matter injury |
title_sort | endothelin 1 endothelin receptor b complex contributes to oligodendrocyte differentiation and myelin deficits during preterm white matter injury |
topic | white matter injury neuron-glia interaction oligodendrocyte precursor cell single-cell RNA sequencing myelination |
url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1163400/full |
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