Arrhythmogenic cardiomyopathy(ACM)is one of the most common inherited cardiomyopathies,characterized by progressive fibrofatty replacement in the myocardium.However,the cellular origin of cardiac adipocytes in ACM rem...Arrhythmogenic cardiomyopathy(ACM)is one of the most common inherited cardiomyopathies,characterized by progressive fibrofatty replacement in the myocardium.However,the cellular origin of cardiac adipocytes in ACM remains largely unknown.Unraveling the cellular source of cardiac adipocytes in ACM would elucidate the underlying pathological process and provide a potential target for therapy.Herein,we generated an ACM mouse model by inactivating desmosomal gene desmoplakin in cardiomyocytes;and examined the adipogenic fates of several cell types in the disease model.The results showed that SOX9^(+),PDGFRa^(+),and PDGFRb^(+)mesenchymal cells,but not cardiomyocytes or smooth muscle cells,contribute to the intramyocardial adipocytes in the ACM model.Mechanistically,Bmp4 was highly expressed in the ACM mouse heart and functionally promoted cardiac mesenchymal-to-adipose transition in vitro.展开更多
The cochlea consists of multiple types of cells,including hair cells,supporting cells and spiral ganglion neurons,and is responsible for converting mechanical forces into electric signals that enable hearing.Genetic a...The cochlea consists of multiple types of cells,including hair cells,supporting cells and spiral ganglion neurons,and is responsible for converting mechanical forces into electric signals that enable hearing.Genetic and environmental factors can result in dysfunctions of cochlear and auditory systems.In recent years,gene therapy has emerged as a promising treatment in animal deafness models.One major challenge of the gene therapy for deafness is to effectively deliver genes to specific cells of cochleae.展开更多
Dear Editor,Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)has caused the COVID-19 pandemic,with more than 528 million infections and 6.2 million deaths.To fight against this rapidly spreading pandemic,pro...Dear Editor,Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)has caused the COVID-19 pandemic,with more than 528 million infections and 6.2 million deaths.To fight against this rapidly spreading pandemic,prophylactic vaccines have been developed using different techniques,such as inactivated virus,messenger RNAs,recombinant proteins,and viral-vectored vaccines.However,rapidly spreading variants of SARS-CoV-2,such as alpha,beta,delta,and omicron variants,have been emerging.展开更多
基金supported by the National key R&D Program of China(2018YFA0108100,2018YFA0108700,2017YFA0105602)the National Natural Science Foundation of China(31871474,81720108004,81974019)+7 种基金the Chinese Postdoctoral Science Foundation(2022M710144)the“Shuguang Program”supported by Shanghai Education Development Foundation and Shanghai Municipal Commission(17SG54)Shanghai Rising-Star Program(20QA1406900,22QA1409300)the Research Team Project of Natural Science Foundation of Guangdong Province of China(2017A030312007)the Science and Technology Planning Project of Guangdong Province(2022B1212010010)the Key Program of Guangzhou Science Research Plan(201904020047)the Special Project of Dengfeng Program of Guangdong Provincial People’s Hospital(DFJH201812,KJ012019119,KJ012019423)the Shanghai Tech University Start-Up Fund。
文摘Arrhythmogenic cardiomyopathy(ACM)is one of the most common inherited cardiomyopathies,characterized by progressive fibrofatty replacement in the myocardium.However,the cellular origin of cardiac adipocytes in ACM remains largely unknown.Unraveling the cellular source of cardiac adipocytes in ACM would elucidate the underlying pathological process and provide a potential target for therapy.Herein,we generated an ACM mouse model by inactivating desmosomal gene desmoplakin in cardiomyocytes;and examined the adipogenic fates of several cell types in the disease model.The results showed that SOX9^(+),PDGFRa^(+),and PDGFRb^(+)mesenchymal cells,but not cardiomyocytes or smooth muscle cells,contribute to the intramyocardial adipocytes in the ACM model.Mechanistically,Bmp4 was highly expressed in the ACM mouse heart and functionally promoted cardiac mesenchymal-to-adipose transition in vitro.
基金We thank the Shanghai Municipal Government and ShanghaiTech University,and the Bioimaging Core Facilities of the iHuman Institute and the animal facility of National Center for Protein Science Shanghai for their financial support.Hao Wu was supported by the Key Project of the National Natural Science Foundation of China(NSFC 81730028)the National Key Technology Research and Development Program of the Ministry of Science and Technology of China(2017YFC1001800)+4 种基金Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases(14DZ2260300)Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)the Innovative Research Team of High-level Local Universities in Shanghai.This work was supported by the National Natural Science Foundation of China(31771130(G.Z.)the 2015 Thousand Youth Talents Plan of China(G.Z.,).This work was supported by the National Natural Science Foundation of China(82122019,Y.T.)the program for professors with special appointments(Eastern Scholar,Y.T.)at Shanghai Institutions of Higher Learning.
文摘The cochlea consists of multiple types of cells,including hair cells,supporting cells and spiral ganglion neurons,and is responsible for converting mechanical forces into electric signals that enable hearing.Genetic and environmental factors can result in dysfunctions of cochlear and auditory systems.In recent years,gene therapy has emerged as a promising treatment in animal deafness models.One major challenge of the gene therapy for deafness is to effectively deliver genes to specific cells of cochleae.
基金supported by Science and Technology Commission of Shanghai Municipality(YDZX20223100001002)Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine at ShanghaiTech University,Shanghai Local College Capacity Building Project(22010502700)+1 种基金grants from the National Key Research and Development Program of China(2017YFC1001301(G.Z.),2019YFA0111000(H.W.))National Natural Science Foundation of China(31871487(C.L.)).
文摘Dear Editor,Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)has caused the COVID-19 pandemic,with more than 528 million infections and 6.2 million deaths.To fight against this rapidly spreading pandemic,prophylactic vaccines have been developed using different techniques,such as inactivated virus,messenger RNAs,recombinant proteins,and viral-vectored vaccines.However,rapidly spreading variants of SARS-CoV-2,such as alpha,beta,delta,and omicron variants,have been emerging.