Post-natal cardiomyocytes can generate iPS cells with an enhanced capacity toward cardiomyogenic re-differentation

Abstract

Adult mammalian cells can be reprogrammed to a pluripotent state by forcing the expression of a few embryonic transcription factors. The resulting induced pluripotent stem (iPS) cells can differentiate into cells of all three germ layers. It is well known that post-natal cardiomyocytes (CMs) lack the capacity to proliferate. Here, we report that neonatal CMs can be reprogrammed to generate iPS cells that express embryonic-specific markers and feature gene-expression profiles similar to those of mouse embryonic stem (mES) cell and cardiac fibroblast (CF)-derived iPS cell populations. CM-derived iPS cells are able to generate chimeric mice and, moreover, re-differentiate toward CMs more efficiently then either CF-derived iPS cells or mES cells. The increased differentiation capacity is possibly related to CM-derived iPS cells retaining an epigenetic memory of the phenotype of their founder cell. CM-derived iPS cells may thus lead to new information on differentiation processes underlying cardiac differentiation and proliferation.

An epigenetic perspective on the failing heart and pluripotent-derived-cardiomyocytes for cell replacement therapy

“…However, when examining successfully derived CMs from either source, they appeared to be functionally equivalent (electrophysiology, calcium handling, therapeutic benefit in mouse MI model). Rizzi et al, similarly demonstrated enhanced CM differentiation efficiency for cardiac-derived-iPSCs in mice, but also observed functional improvement relative to CMs from fibroblastiPSCs (calcium handling) (Rizzi et al, 2012). Besides the obvious differences in species (human vs mouse), SanchezFreire et al ultized CPs rather than CMs for initial iPSC generation.…”

Inhibition of H3K9 histone methyltransferase G9a attenuates renal fibrosis and retains klotho expression

“…[34][35][36][37] Methylation of lysine 9 of histone H3 (H3K9) is associated with euchromatin gene silencing via binding of heterochromatin protein-1. 38 Among the histone modification enzymes, the histone lysine methyltransferase G9a (also known as euchromatic histone lysine N-methyltransferase 2) is a key enzyme for H3K9 mono-and dimethylation (me1 and me2).…”

MicroRNAs Contribute to Induced Pluripotent Stem Cell Somatic Donor Memory

“…The relevance of transcriptional regulators in the context of epigenetic memory following reprogramming in HPCs has been already reported (7)(8)(9)12). Using CD34ϩ HPCs as a model, DNA microarray analysis data combined with genomewide methylation assays suggested that promoter DNA demethylation might play a role in genome-wide gene regulation within the hematopoietic compartment after the reprogramming and differentiation processes.…”