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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Main Authors: Mengjie Du, Na Wang, Xiaolong Xin, Chun-Lan Yan, Yan Gu, Liang Wang, Ying Shen
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
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.
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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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