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Single-cell analysis reveals an Angpt4-initiated epdc-EC-CM cellular coordination cascade during heart regeneration

Protein & Cell 2023年第5期14卷 350-368页

作者： Zekai Wu Yuan Shi Yueli Cui Xin Xing Liya Zhang Da Liu Yutian Zhang Ji Dong Li Jin Meijun Pang Rui-Ping Xiao Zuoyan Zhu Jing-Wei Xiong Xiangjun Tong Yan Zhang Shiqiang Wang Fuchou Tang Bo Zhang Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education Peking University Genome Editing Research CenterCollege of Life SciencesPeking UniversityBeijing 100871China Beijing Advanced Innovation Center for Genomics(ICG) College of Life SciencesPeking UniversityBeijing 100871China State Key Laboratory of Membrane Biology Institute of Molecular MedicineCollege of Future TechnologyPeking UniversityBeijing 100871China State Key Laboratory of Membrane Biology College of Life SciencesPeking UniversityBeijing 100871China Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences School of Basic Medical SciencesMinistry of EducationPeking University Health Science CenterBeijing 100191China Institute of Molecular Medicine College of Future TechnologyPeking UniversityBeijing 100871China

Mammals exhibit limited heart regeneration ability,which can lead to heart failure after myocardial *** contrast,zebrafish exhibit remarkable cardiac regeneration *** cell types and signaling pathways have been reported to participate in this ***,a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is *** collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury *** revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes,and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during ***,we identified a regeneration-induced cell(RIC)population in the epicardium-derived cells(epdc),and demonstrated Angiopoietin 4(Angpt4)as a specific regulator of heart ***4 expression is specifically and transiently activated in RIC,which initiates a signaling cascade from epdc to endocardium through the Tie2-MAPK pathway,and further induces activation of cathepsin K in cardiomyocytes through RA *** of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation,while overexpression of angpt4 accelerates ***,we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes,and promote cardiac repair in mice after myocardial infarction,indicating that the function of Angpt4 is conserved in *** study provides a mechanistic understanding of heart regeneration at single-cell precision,identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration,and offers a novel therapeutic target for improved recovery after human heart injuries.

关键词： scRNA-seq zebrafish heart regeneration Angpt4 epdc

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日本内阁决定让epdc私有化

引用

国外核新闻 1997年第11期 6-页

作者：卜灵

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