Abstract
Epigenetics regulations have an important role in fertilization and proper embryonic development, and several human diseases are associated with epigenetic modification disorders, such as Rett syndrome, Beckwith-Wiedemann syndrome and Angelman syndrome. However, the dynamics and functions of long non-coding RNAs (lncRNAs), one type of epigenetic regulators, in human pre-implantation development have not yet been demonstrated. In this study, a comprehensive analysis of human and mouse early-stage embryonic lncRNAs was performed based on public single-cell RNA sequencing data. Expression profile analysis revealed that lncRNAs are expressed in a developmental stage–specific manner during human early-stage embryonic development, whereas a more temporal-specific expression pattern was identified in mouse embryos. Weighted gene co-expression network analysis suggested that lncRNAs involved in human early-stage embryonic development are associated with several important functions and processes, such as oocyte maturation, zygotic genome activation and mitochondrial functions. We also found that the network of lncRNAs involved in zygotic genome activation was highly preservative between human and mouse embryos, whereas in other stages no strong correlation between human and mouse embryo was observed. This study provides insight into the molecular mechanism underlying lncRNA involvement in human pre-implantation embryonic development.
Highlights
Understanding human pre-implantation development can provides insight into common human birth defects and improve our understanding of the pathogenic mechanisms of many complex diseases such as Rett syndrome, Beckwith-Wiedemann syndrome and Angelman syndrome [1, 2]
Weighted gene co-expression network analysis suggested that long non-coding RNAs (lncRNAs) involved in human early-stage embryonic development are associated with several important functions and processes, such as oocyte maturation, zygotic genome activation and mitochondrial functions
All reads of the 90 single-cell RNA sequencing (RNA-seq) datasets (GSE36552) were aligned to the human genome using HISAT, and the details of the mapping results are shown in Supplementary Table S1
Summary
Understanding human pre-implantation development can provides insight into common human birth defects and improve our understanding of the pathogenic mechanisms of many complex diseases such as Rett syndrome, Beckwith-Wiedemann syndrome and Angelman syndrome [1, 2]. Members of numerous non-coding RNA classes are expressed in the oocyte and pre-implantation embryo, and they have have an important role in fertilization and proper embryonic development [3], including directing cell fate decisions and cell differentiation during embryogenesis, which involves the formation of highly complex tissues comprised of many different cell types with specific and stable gene expression patterns [4]. Long non-coding RNAs (lncRNAs), which are typically over 200 nucleotides in length , are involved in the cleavage stage of embryonic development [6]. A large number of human developmental disorders are related to the abnormal expression of some lncRNAs, such as DBE-T in facioscapulohumeral muscular dystrophy, SNORD115 and SNORD116 in Prader-Willi Syndrome and KCNQ1OT1 and H19 in Beckwith-Wiedemann Syndrome and Silver-Russell Syndrome, which suggests that lncRNAs may play an important role in pre-implantation development [9,10,11]. The expression profiles and the regulation mechanism of lncRNAs in human earlystage embryos remain unclear
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