Identification of juvenility-associated genes in the mouse hepatocytes and cardiomyocytes

Abstract

Young individuals possess distinct properties that adults do not. The juvenile animals show higher activities for growth, healing, learning and plasticity than adults. The machinery for establishing these juvenile properties is not fully understood. To better understand the molecular constituents for the above properties, we performed a comprehensive transcriptome analysis of differently aged cells of mice by high-throughput sequencing and identified the genes selectively highly expressed in the young cells. These genes, collectively called as juvenility-associated genes (JAGs), show significant enrichments in the functions such as alternative splicing, phosphorylation and extracellular matrix (ECM). This implies the juvenescence might be achieved by these functions at the cell level. The JAG mutations are associated with progeria syndromes and growth disorders. Thus, the JAGs might organize the juvenile property of young animals and analysis of JAGs may provide scientific and therapeutic approaches toward treating the genetic diseases.

Figure 1

Transcriptome analysis reveals specific gene sets expressed in juvenile hepatocytes and cardiomyocytes in mice. (A) A schematic describing the identification of juvenility-associated genes (JAGs). Hepato-, hepatocyte. Cardio-, cardiomyocyte. P, postnatal day. (B) Heatmap analysis of the transcriptome analysis in the hepatocytes and the cardiomyocytes of mice at different ages. (C) Examples of a constitutively expressed gene (Beta2-Microglobulin), a hepato-JAG (IGFBP2), a cardio-JAG (Pleiotrophin) and a common JAG (Glypican3).

Figure 2

The hepato-JAGs exhibit a distinct gene expression profile. (A) Filtration and identification of hepato-JAGs from the comprehensive transcriptome analysis in the hepatocytes of the differently-aged mice. (B) The gene ontology (GO) analysis with the hepato-JAGs. GO CC, gene ontology cellular component. Ubl, ubiquitin and ubiquitin-like. (C) The gene set enrichment analysis (GSEA) with the transcriptome in the hepatocytes. NES, normalized enrichment score. FDR, false discovery rate. (D) The STRING network analysis with the extracellular matrix (ECM)-associated hepato-JAGs. (E) The hepato-JAGs discovered among the genes reported by Jia et al. to be causative for the hepatoblastoma.

Figure 3

Maturation dynamics in the hepatocytes. (A) Heatmap analysis of transcriptome analysis in the hepatocytes at different ages. The distinct sets of genes were present as noted as P1-, P7- and P56-associated genes. (B) The GO analysis describing the transition of cellular functions in the hepatocytes. GO BP, gene ontology biological process. (C) A schematic for the transition of the cellular functions in the postnatal hepatocytes.

Figure 4

The cardio-JAGs exhibit a distinct gene expression profile. (A) Filtration and identification of cardio-JAGs from the comprehensive transcriptome analysis in the cardiomyocytes of the differently-aged mice. (B) The GO analysis with the cardio-JAGs. (C) The GSEA with the transcriptome in the cardiomyocytes. (D) The STRING network analysis with the extracellular matrix (ECM)-associated cardio-JAGs.

Figure 5

Maturation dynamics in the cardiomyocytes. (A) Heatmap analysis of transcriptome analysis in the cardiomyocytes at different ages. The distinct sets of genes were present as noted as P1-, P7- and P56-associated genes. (B) The GO analysis describing the transition of cellular functions in the cardiomyocytes. (C) A schematic for the transition of the cellular functions in the postnatal cardiomyocytes.

Figure 6

The common JAGs exhibit a distinct gene expression profile. (A) The Venn diagram showing the common JAGs as overlapping genes between the hepato-JAGs and the cardio-JAGs. (B) The GO analysis with the common JAGs. (C) The cellular functions that constitute the juvenile properties at the cell level.

Figure 7

Associations of the common JAGs to the human genetic diseases. Biological categories of the genes and their associated human genetic diseases. All the common JAGs were searched for their association with human genetic diseases.