Whole-transcriptome analysis identifies re-expression of fetal splice variants in cardiac hypertrophy

Cardiac hypertrophy has been well-characterized at the level of transcription. During cardiac hypertrophy, genes normally expressed primarily during fetal heart development are re-expressed, and this fetal gene program is believed to be a critical component of the hypertrophic process. Recently, alternative splicing of mRNA transcripts has been shown to be temporally regulated during heart development, leading us to consider whether fetal patterns of splicing also reappear during hypertrophy.We hypothesized that patterns of alternative splicing occurring during heart development are recapitulated during cardiac hypertrophy. Here we present a whole-transcriptome study of isoform expression during pressure-overload cardiac hypertrophy induced by 10 days of transverse aortic constriction (TAC) in rats and in developing fetal rat hearts compared to sham-operated adult rat hearts, using high-throughput sequencing of poly(A) tail mRNA.心脏肥大（cardiac hypertrophy）在转录层面已得到充分表征。在心脏肥大进程中，通常仅在胎儿心脏发育阶段表达的基因会被重新激活，而该胎儿基因程序被认为是肥大过程的关键组成部分。近年来，研究证实mRNA转录本的可变剪接（alternative splicing）在心脏发育过程中受时序调控，这促使我们思考：肥大过程中是否也会重现胎儿时期的剪接模式？我们提出假说：心脏发育过程中出现的可变剪接模式，会在心脏肥大时得到重现。本研究通过对聚腺苷酸尾mRNA（poly(A) tail mRNA）开展高通量测序（high-throughput sequencing），针对大鼠经10天主动脉弓缩窄（transverse aortic constriction, TAC）诱导的压力负荷型心脏肥大模型、发育中的胎鼠心脏，并以假手术成年大鼠心脏作为对照，开展了全转录组（whole-transcriptome）水平的转录本异构体（isoform）表达分析。