SSingle cell systems biology of long non-coding RNAs associated with cardiac tissue development and cardiovascular disease
Long non-coding RNAs, Single-cell, Heart development, Cardiovascular disease, Machine learning, Cardiomyocyte subpopulation.
Long non-coding RNAs (lncRNAs) comprise the most representative transcriptional units of the mammalian genome, and they’re associated with organ development that can be associated with the emergence of diseases, such as cardiovascular diseases. The World Health Organization (WHO), for example, has published that cardiovascular diseases are responsible for the death of 17.9 million people each year, corresponding to 31% of all deaths all around the world. Therefore, a combination of transcripts from Gencode (M20), Ensembl (GRCm38.95) and Amaral et al. (2018) databases was used to define the set of non-redundant reference lncRNAs; and Gencode (M20) for the reference coding transcripts. In addition, bioinformatics approaches, machine learning algorithms and statistical techniques were used to define lncRNAs involved in mammalian cardiac development in a single-cell perspective. For this, the single-cell database published by DeLaughter et al. (2016) was used, in which there were data from 4 embryonic stages (E9.5, E11.5, E14.5, E18.5) and 4 post -natals (P0, P3, P7, P21) of the mus musculus model organism. Our study identified 8 distinct cell types, novel marker transcripts (coding/lncRNAs) and also, differential expression and functional enrichment analysis revealed cardiomyocyte subpopulations associated with cardiac function; meanwhile modular co-expression analysis reveals cell-specific functional insights for lncRNAs during myocardial development, including a potential association with key genes related to disease and the “fetal gene program”. Our results evidence the role of particular lncRNAs in heart development, and highlights the usage of co-expression modular approaches in the cell-type functional definition. As future work, we intend to identify the functional roles of these RNAs in the development of cardiac tissues and in cardiovascular diseases using experimental validation approaches.