Heart disease stands as the foremost global cause of mortality.In rodents,the heart possesses the remarkable ability for cardiac regeneration within the first 7 days post-birth.Furthermore,the transition to an oxygen-...Heart disease stands as the foremost global cause of mortality.In rodents,the heart possesses the remarkable ability for cardiac regeneration within the first 7 days post-birth.Furthermore,the transition to an oxygen-rich environment and altered nutrient availability trigger a profound shift in cardiac energy metabolism immediately after birth.Lactylation,which translates metabolic adjustments into enduring gene expression patterns,has been recognized for its role in this process.However,its role in heart development has remained unexplored.In this study,we conduct an integrated study combining global proteomics,lactylome,and genome-wide RNA sequencing to elucidate the role of lactylation throughout postnatal heart development.Our findings demonstrate a remarkable increase in non-histone lactylation levels as early as 1 week(1 w)to 6 weeks(6 w)postpartum and remained elevated from 6 months(6 m)onwards.However,the histone lactylation showed the opposite trend.Additionally,we propose that histone 4 lysine 12 lactylation(H4K12la)acts as a pivotal upstream regulatory element in the early postnatal mouse heart,from 1 w to 6 w postpartum.Our findings strongly suggest a significant connection between lactylation and postnatal cardiac development and highlight its involvement in gene expression regulation,thus offering potential mechanisms for targeting heart diseases.展开更多
基金funded by National Key Research and Development Program Funding(2023YFC3605504,to X.L)National High-Level Hospital Clinical Research Funding(2022-PUMCHB-098,to S.Z)+3 种基金National Natural Science Foundation of China(22277125 and 92253306 to H.H.)Natural Science Foundation of Shanghai(23ZR1474600 to H.H.)Shanghai Municipal Science and Technology Major Project(to H.H.)Tsinghua-Peking Center for Life Sciences(045-61020100123,to S.Z.).
文摘Heart disease stands as the foremost global cause of mortality.In rodents,the heart possesses the remarkable ability for cardiac regeneration within the first 7 days post-birth.Furthermore,the transition to an oxygen-rich environment and altered nutrient availability trigger a profound shift in cardiac energy metabolism immediately after birth.Lactylation,which translates metabolic adjustments into enduring gene expression patterns,has been recognized for its role in this process.However,its role in heart development has remained unexplored.In this study,we conduct an integrated study combining global proteomics,lactylome,and genome-wide RNA sequencing to elucidate the role of lactylation throughout postnatal heart development.Our findings demonstrate a remarkable increase in non-histone lactylation levels as early as 1 week(1 w)to 6 weeks(6 w)postpartum and remained elevated from 6 months(6 m)onwards.However,the histone lactylation showed the opposite trend.Additionally,we propose that histone 4 lysine 12 lactylation(H4K12la)acts as a pivotal upstream regulatory element in the early postnatal mouse heart,from 1 w to 6 w postpartum.Our findings strongly suggest a significant connection between lactylation and postnatal cardiac development and highlight its involvement in gene expression regulation,thus offering potential mechanisms for targeting heart diseases.
