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. 2017 May 3:12:136-145.
doi: 10.1016/j.gdata.2017.05.006. eCollection 2017 Jun.

Dynamic regulation of small RNAome during the early stage of cardiac differentiation from pluripotent embryonic stem cells

Yue Li  1   2 , An Zeng  1 , Ge Li  1 , Ya-Na Guan  1 , Huang-Tian Yang  1 , Bairong Shen  3 , Qing Jing  1   2
Affiliations

Dynamic regulation of small RNAome during the early stage of cardiac differentiation from pluripotent embryonic stem cells

Yue Li et al. Genom Data. .

Abstract

Embryonic stem cells (mESCs), having potential to differentiate into three germ-layer cells including cardiomyocytes, shall be a perfect model to help understanding heart development. Here, using small RNA deep sequencing, we studied the small RNAome in the early stage of mouse cardiac differentiation. We found that the expression pattern of most microRNA (miRNA) were highly enriched at the beginning and declined thereafter, some were still insufficiently expressed on day 6, and most miRNAs recovered in the following days. When pluripotent embryonic stem cells are differentiating to cardiomyocytes, targeted genes are concentrated on TGF, WNT and cytoskeletal remodeling pathway. The pathway and network of dynamically changed target genes of the miRNAs at different time points were also investigated. Furthermore, we demonstrated that small rDNA-derived RNAs (srRNAs) were significantly up-regulated during differentiation, especially in stem cells. The pathways of srRNAs targeted genes were also presented. We described the existence and the differential expression of transfer RNA (tRNA), Piwi-interacting RNA (piRNA) and Endogenous siRNAs (endo-siRNAs) in this process. This study reports the genome-wide small RNAome profile, and provides a uniquely comprehensive view of the small RNA regulatory network that governs embryonic stem cell differentiation and cardiac development.

Keywords: Cardiac differentiation; Deep sequencing; Murine embryonic stem cells; Pathway enrichment; Regulatory networks; Small RNAs.

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Figures

Fig. 1
Fig. 1
Heatmap and four main change patterns of miRNAs. (A) Highly enriched on D0. (B) Down-regulated on D2. (C) Down-regulated on D2 and D6. (D) Up-regulated on D9.
Fig. 2
Fig. 2
The TGF, WNT and cytoskeletal remodeling pathway.
Fig. 3
Fig. 3
Networks of genes during cardiac differentiation of mESCs. The triangle nodes represent dynamically changed miRNAs, while the circle nodes refer to the target genes of miRNAs. Edges denote interactions/associations between genes and miRNAs. (A) Targets of highly enriched miRNAs on D0. (B) Targets of down-regulated miRNAs on D2. (C) Targets of down-regulated miRNAs on D2 and D6. (D) Targets of up-regulated miRNAs on D9.
Fig. 4
Fig. 4
The expression pattern of srRNAs on D0, D2, D6 and D9. (A) The percentage of srRNAs in small RNAs. (B) Length distribution of total redundant srRNAs. (C) Length distribution of unique srRNAs. (D) Profiling of most abundantly expressed srRNAs.
Fig. 5
Fig. 5
Positions of srRNAs in different type of ribosomal RNAs. (A) 28S. (B) Normalized reads counts of 28s-1-21, 28s-1-19 on day 0, day 2, day 6 and day 9. (C) 5S. (D) 5.8S (E) 18S.
Fig. 6
Fig. 6
Diagram of endogenous siRNA. (A) siRNA-0001. (B) siRNA-0002. (C) siRNAs-0003. (D) siRNA-0004.
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