Cardiac regeneration may revolutionize treatment for heart failure but endogenous progenitor-derived cardiomyocytes in the adult mammalian heart are few and pre-existing adult cardiomyocytes divide only at very low rates. Although candidate genes that control cardiomyocyte cell cycle re-entry have been implicated, expression heterogeneity in the cardiomyocyte stress-response has never been explored. Here, we show by single nuclear RNA-sequencing of cardiomyocytes from both mouse and human failing, and non-failing adult hearts that sub-populations of cardiomyocytes upregulate cell cycle activators and inhibitors consequent to the stress-response in vivo. We characterize these subgroups by weighted gene co-expression network analysis and discover long intergenic non-coding RNAs (lincRNA) as key nodal regulators. KD of nodal lincRNAs affects expression levels of genes related to dedifferentiation and cell cycle, within the same gene regulatory network. Our study reveals that sub-populations of adult cardiomyocytes may have a unique endogenous potential for cardiac regeneration in vivo.

Malaria remains to be a global problem and has caused approximately 700,000 deaths per year. Plasmodium falciparum (P. falciparum) is a eukaryotic apicomplexan parasite and is one of the causative agents of malaria. The transcriptome of P. falciparum during the intraerythrocytic developmental cycle (IDC) is characterized by a highly regulated cascade of transcripts where 60-80% of the 5500 genes in the parasite genome are expressed at least once. However, mechanisms of transcriptional control are not well characterized in P. falciparum. In particular, there is a lack of functional cis-regulatory DNA motifs described in P. falciparum. We have utilized an algorithm to predict DNA motifs on co-regulated genes and tested their functionality by transfection assays. Interestingly, we have found an overrepresentation of motifs which repress transcription. We have also found that the repressive effects of several of motifs were stage specific and regulate transcription of groups of genes. Hence, this leads us to propose repression of transcription as a form of transcriptional regulation in P. falciparum.