A new study led by researchers at Peking Union Medical College Hospital and the Shanghai Institute of Materia Medica has used multi-omics analysis to explore the role of lysine lactylation in heart development. The research found that lysine lactylation, a type of epigenetic modification, plays a crucial role in regulating gene expression and influencing the development and maturation of heart tissue.
A recent study led by Dr. Xiaodong Luan from the Institute of Clinical Medicine at Peking Union Medical College Hospital, Dr. Shuyang Zhang from the Department of Rare Diseases at Peking Union Medical College Hospital, and Dr. He Huang from the Shanghai Institute of Materia Medica, Chinese Academy of Science s, has shed light on the intricate molecular mechanisms governing postnatal heart development.
Utilizing a comprehensive multi-omics approach encompassing global proteomics, lactylome profiling, and genome-wide RNA sequencing (RNA-seq), the researchers meticulously examined the molecular changes occurring across various developmental stages.Their findings revealed significant alterations in proteins, lactylation patterns, and gene expression levels related to energy and nucleic acid metabolism during the crucial early postpartum period, spanning from 1 to 6 weeks after birth. These alterations stabilized after 6 weeks, suggesting a dynamic shift in metabolic processes during this critical developmental window. Intriguingly, the team observed a progressive accumulation of non-histone lactylation levels from 1 week to 6 months, while histone lactylation levels decreased rapidly during the first 6 weeks postpartum. This divergence in lactylation patterns between histones and non-histones highlights the complex interplay of epigenetic modifications in heart development.Further analysis of differentially expressed proteins between the 1-week and 6-week mouse heart revealed an upregulation of proteins involved in the TCA cycle and respiratory electron transport pathways, indicating an increase in energy metabolism during this period. Conversely, proteins involved in the processing of capped intron-containing pre-mRNA were significantly downregulated, suggesting a shift towards a more mature transcriptional profile. Notably, the adolescent mouse heart exhibited elevated levels of developmental, morphogenetic, and metabolic processes, including cellular response to chemical stimuli, organic acid metabolism, energy generation, muscle system processes, developmental regulation, and lipid biosynthesis. Conversely, nucleic acid metabolism pathways, such as cell cycle, nuclear division, chromosome segregation, and DNA replication, were downregulated, reflecting a transition towards a less proliferative state. These findings contribute valuable insights into the molecular underpinnings of heart development and provide potential targets for therapeutic interventions aimed at promoting cardiac regeneration
Cardiac Development Lysine Lactylation Epigenetics Multi-Omics Heart Regeneration
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